- Email: [email protected]
Radiolabeled Theranostics
C H A P T E R
25 Radiolabeled Theranostics: Magnetic and Gold Hybrid Nanoparticles Ayuob Aghanejad1 and Yadollah Omidi1,2 1
Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran 2Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
25.1 INTRODUCTION Hybrid nanoparticles (HNPs) composed of a targeting agent such as antibody (Ab) or aptamer (Ap), imaging agent (e.g., radionuclide, fluorophore), and therapeutic agent have been developed as theranostic nanocarriers for targeted detection and therapy. Several types of HNPs (e.g., metal/metal oxide, polymer/metal, metal/graphene, lipid/ polymer, radioisotope/metal, etc.) have extensively been explored for the development of improved drug delivery systems (DDSs) with maximal therapeutic effects and minimal side effects [1 3]. The physicochemical features (e.g., morphology, size, surface area, multivalency, and unique optical characteristics) of various metal-based NPs, in particular, gold NPs (AuNPs) and magnetic NPs (MNPs), have widely been exploited to improve the efficiency of target-guided imaging/therapy molecular probes [4]. Further, so far a number of diagnostic procedures has been used for simultaneous diagnosis and therapy of diseases/malignancies using theranostics. Among them, nuclear imaging approach using radiolabeled tracers has been well-established in medical practice and research for decades [5,6]. Various radiolabeled NPs have been employed as hybrid NSs. Accordingly, a number of potent diagnostic modalities, whose applications depend on the radionuclide’s property, has been used as hybrid NPs in imaging techniques such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET) [7]. Overall, the potential of radioisotope-containing NPs (i.e., radiolabeled HNPs) in the accurate medical imaging procedures make them very valuable diagnostic and therapeutic agents. Moreover, radiolabeled hybrid NPs (RHNPs) provide great
Noble Metal-Metal Oxide Hybrid Nanoparticles DOI: https://doi.org/10.1016/B978-0-12-814134-2.00025-5
535
© 2019 Elsevier Inc. All rights reserved.
536
25. RADIOLABELED THERANOSTICS: MAGNETIC AND GOLD HYBRID NANOPARTICLES
TABLE 25.1 Selected Targeted Nanohybrids for PET and SPECT Imaging Nanohybrid
Radionuclide Half-life
Targeting Agent
Application
Ref.
Magnetic
64
12.70 h
C-type atrial natriuretic factor peptide
PET imaging of prostate cancer cells
[9]
59.49 d
3H11 mAb
SPECT/MR imaging of gastric cancer models
[10]
6.02 h
Cyclic Arg Gly Asp DPhe Lys (cRGDfK) peptide
SPECT/MR imaging of glioblastoma
[11]
78.41 h
Cetuximab
PET imaging of the epidermal cancer
[12]
Tc
6.02 h
GGC peptide
SPECT imaging of lymph node
[13]
I
59.49 d
cRGD peptide
SPECT/CT imaging of small cell lung cancer models
[14]
Cu
125
I
99m
Gold
89
Tc
Zr
99m 125
possibility for whole-body imaging with high quantitative and sensitivity, and hence are considered as one of the most reliable and robust methods for the in vitro and in vivo molecular imaging [8]. Table 25.1 shows some selected radiolabeled nanohybrids used for CT, SPECT, PET, and MR imaging. In fact, development of molecular nanoprobes for the target-guided imagining of biological events in the living body without any disruption at molecular and cellular levels can remarkably be beneficial not only for the detection of disease mechanisms but also for the improvement of targeted therapy of designated cells/tissue, in particular in different types of solid tumors.
25.2 IMAGING MODALITIES Different imaging modalities such as isotopic PET and SPECT imaging, computed tomography (CT), and magnetic resonance imaging (MRI), as well as optical imaging by means of various fluorophores have been employed for the accurate diagnosis of a number of formidable diseases, such as malignancies.
25.2.1 PET and SPECT Imaging Systems Undoubtedly, PET is one of the most valuable quantitative imaging technologies with the great detection ability of abnormalities at the molecular and cellular levels [15,16]. In this molecular imaging system, extremely minimized doses of the radiopharmaceuticals with high specific activity are used to acquire high-resolution images—an imaging process that is considered to be safe to other healthy tissues/organs [17,18]. SPECT is another interesting technique with unique features that can be employed for the imaging of emerging biological phenomena at molecular/cellular levels. In addition,
II. APPLICATIONS
25.3 RADIOLABELED HYBRID AuNPs
537
the progression of malignancy, infections, or inflammations and even the delivery of radiopharmaceuticals have been imaged by SPECT and hybrid imaging techniques such as SPECT/CT [19,20]. Moreover, PET, SPECT, and their hybrid imaging systems (e.g., MRI CT hybrid imaging system) were shown to have significant potential in the simultaneous detection of various biological functions. For the probing of different molecular processes by these imaging systems, NP-based probes have successfully been used for multimodal bioimaging using radioisotopes with different emission energies [21,22].
25.2.2 MRI, CT, and Optical Imaging Systems MRI is a nonionization approach, which spots water molecules in the tissues/organs at a magnetic field. This imaging approach has a significant potential for the detection and status of diseases such as tumor progression and even responses to treatment modalities. So far, a number of contrast agents (e.g., MNPs and hybrid NPs) have been used for the implementation of this powerful diagnostic technique [23]. CT as a diagnostic and costeffective tool has been developed for the X-ray-based monitoring of various diseases including different types of solid tumors. Currently, the most common contrast agents of CT are surprisingly used nonspecifically. They are not able to target the desired cells/tissues specifically, failing to detect cancer biomarkers and biological components. Additionally, different types of optical imaging methods based on hybrid NPs (e.g., nearinfrared, fluorescence, etc.) have been developed for monitoring of the biological events, in large part due to their significant complementary imaging features [24,25]. Hence, to provide images with significantly high specificity and resolution, the multimodal imaging systems which merge functional imaging techniques (e.g., SPECT, PET) with anatomically three-dimensional (3D) modalities (e.g., CT, MRI) can be effectively employed and result in improved imaging in comparison with the single modality operating systems [26,27]. The PET CT/MRI and SPECT CT, as remarkable dual-modality imaging techniques, have been employed to improve the medical applications, particularly in diagnosis and therapy of cancers, providing much more functional information, an enhanced soft-tissue contrast, and a lower radiation exposure [28,29]. Fig. 25.1 represents different imaging techniques and multimodal nanohybrids (NHs) as imaging agents.
25.3 RADIOLABELED HYBRID AuNPs Recently, various types of NHs such as superparamagnetic nanoparticles (SPIONs), quantum dots (QDs), and AuNPs have been developed for targeted molecular detection of tumor cell/organs. The promising potential of NPs for functionalization with various ligands make them unique tools for a target-guided imaging. Different moieties can be conjugated to NPs/NHs, including antibodies (Abs), aptamers (Aps), peptides, nucleic acids, and proteins. Based on these facts, radiolabeled functionalized metal NPs, such as magnetic/gold NPs, as imaging probes play an important role in cancer detection by PET, SPECT, and their combined imaging modalities (e.g., SPECT/MR, PET/MR, SPECT/CT, and PET/CT), resulting in reliable information about the cellular and molecular
II. APPLICATIONS
538
25. RADIOLABELED THERANOSTICS: MAGNETIC AND GOLD HYBRID NANOPARTICLES
FIGURE 25.1 Radiolabeled nanohybrids (NHs) for multimodality in vitro and in vivo targeted imaging of cancer. (A) Schematic representation of a radiolabeled nanohybrid conjugated with targeting agent. (B) Various imaging techniques for the diagnosis of cancer. SPECT: Single-photon emission computed tomography; PET: Positronemission tomography; CT: Computed tomography; MRI: Magnetic resonance imaging.
interactions from increasing the signal to noise ratios in desired organs/cells [30,31]. These RHNPs are able to target the diseased organs/cells and provide comprehensive physiologic data in both in vivo and in vitro for diagnosis and treatment of cancers.
25.3.1 Radiolabeled Hybrid AuNPs for PET Imaging The AuNPs distinctive physicochemical properties (e.g., biocompatibility, large surface area, and high stability and photoacoustic features) make them as significant NHs for biomedical applications. Various gold-based nanostructures have been preclinically investigated for imaging/therapy in the cancer cells/tissue, including nanocages, nanoshells, nanorods, and nanospheres [32]. Biologically, the AuNPs are considered as nontoxic and inert materials, which can be used for passive and/or active targeting of desired cell/ organs. PET imaging by means of radiolabeled AuNPs at the target cell/tissue provides key quantitative molecular/cellular imaging information on the diseases with high sensitivity and efficiency. In one study, PET/CT imaging of dendritic cell (DC) using adenine-rich oligonucleotide conjugated 124I-AuNPs was performed for tracking of the DCs migration towards lymph nodes. The DCs were labeled with radionuclide-grafted AuNps and their antitumor immune responses examined in mice models. Interestingly, the results revealed the mice that immunized with Lewis lung carcinoma (LLC) lysates and labeled DCs exhibited a strong antitumor activity [33]. In another study, the 64Cu-labeled gold nanoclusters (NCs) functionalized with plerixafor (AMD3100) were used for the detection of the CXCR4 upregulation in the lung metastasis and primary tumors in the breast cancer models using PET imaging. These radiopharmaceuticals provided great capability for the specific detection of tumors expressing CXCR4, which were then proposed as a target-specific RHNPs for the early and accurate detection of the breast cancer with lung metastasis [34]. The 68Ga-labeled gold NHs (AnNHs) are the dual-modality PET/surface-enhanced resonance Raman scattering (SERRS) imaging probe that was developed for the imaging of both pre-operative and intraoperative profile of diseased lymph nodes. As a result, these
II. APPLICATIONS
25.3 RADIOLABELED HYBRID AuNPs
539
PET SERRS nanohybrids were proposed for the tracking of lymph node, and hence, imaging of the status of the disease after treatment strategies [35]. In one study, PET/CT imaging by means of 64Cu-labeled PEGylated AuNHs was developed for the tracking of T cells in patients with B-cells’ malignancy. For this purpose, the T cells were modified with a CD19 specific chimeric antigen receptor (CAR) and the firefly luciferase (ffLuc) through electrotransferring of DNA plasmids. As a result, these PEGylated GNP 64Cu were proposed as a target-specific radiolabeled NHs for the detection and immunotherapy of cancer [36]. In another study, the PEGylated AuNPs were conjugated with arginylglycylaspartic acid (RGD) peptide and radiolabeled with 68Ga. The NH was then used as PET/MRI imaging tracer to study the overexpressing integrin αvβ3 receptor in U87MG cancer cells. The NHs showed specific accumulation in the U87MG glioma cells and appear to offer efficient potentials for integrin-related tumor imaging [37]. Similarly, the PEGylated hollow AuNPs were radiolabeled with 64Cu and decorated with cyclic RGD to develop a target-guided PET/CT imaging agent. The engineered NHs were examined for intratumor accumulation on the VX2 tumor-bearing rabbits, resulting in specifically targeting of the integrin αvβ3 expressing tissues/cells [38].
25.3.2 Radiolabeled Hybrid AuNPs for SPECT Imaging To investigate the vulnerability of atherosclerotic plaques, in a study, the technetium99m labeled AuNPs were conjugated with Annexin V and used as targeted dual modality SPECT/CT imaging nanoprobe. The engineered AuNHs were shown to serve as a potential radiopharmaceutical for specific diagnosis of apoptotic macrophages in ApoE knockout mice by means of SPECT/CT system [39]. In another study, to provide SPECT nanotracer, AuNPs were functionalized with bombesin (BBN) peptide and labeled with 67Ga and used for the preclinical studies on prostate tumor-bearing mice. These NHs were reported to be largely taken up by the gastrinreleasing peptide (GRP) receptor-expressing tumor cells. In the prostate tumor-bearing mice, an intraperitoneal administration of the NHs resulted in pancreas uptake due to the GRP receptor-mediated mechanism, while the enhanced permeability and retention (EPR) effect seemed to play the major role in the intravenous administration. Taken together, these NHs were proposed to serve as promising radiotracers for imaging of cancer cells [40]. Auger electron-emission is an effective approach for the diagnosis and therapy of diseases such as malignancies. In a study, the PEGlyted 125I AuNHs were developed to serve as a diagnostic and therapeutic agent for the delivery of radionuclides to the neoplasms. Based on the Auger-electron energies, these NHs showed a great potential for the imaging and therapy of cancer cells [41]. It should be noted that targeted radionuclide therapy of solid tumors provides the delivery of a high dose of radioactivity to target cells/tissues with decreased side effects to the surrounding normal tissues, and is considered as one of the important strategies for the detection and therapy of cancer cells/tissues. In a study, indium-111 (111In)-labeled PEGylated epidermal growth factor (EGF)-armed AuNHs were engineered to serve as a
II. APPLICATIONS
540
25. RADIOLABELED THERANOSTICS: MAGNETIC AND GOLD HYBRID NANOPARTICLES
FIGURE 25.2 The whole-body SPECT images in xenograft mice bearing 231-H2N (H2N) and MDA-MB-468 (468) tumors 72 h after injection of 111In-Au-EGF, 111In-Au-EGF-PEG6000 and 111In-Au-EGF-PEG6000 plus 30 μg or 15 μg of EGF bulking dosages (T: tumor; S: spleen; L: liver; K: kidney; B: bladder). Source: Image was adapted with permission from a published work conducted by L. Song, S. Able, E. Johnson, K.A. Vallis, Accumulation of (1 1 1) Inlabelled EGF-Au-PEG nanoparticles in EGFR-positive tumours is enhanced by coadministration of targeting ligand, Nanotheranostics 1 (2017) 232 243.
potential radiopharmaceutical for the detection of EGFR-positive breast cancer. The in vivo micro-SPECT/CT studies of the engineered nanosystem (NS) showed somewhat liver uptake with limited tumor accumulation, in large part because of the moderate expression of EGFR by the hepatocytes as well as the rapid clearance of NSs through the mononuclear phagocyte system. The coadministration of unlabeled EGF to reduce the liver uptake might enhance the accumulation of the NSs in the tumor sites. As a result, these NHs were proposed as the target-specific radiolabeled NSs for the detection of EGFR-positive cancer (Fig. 25.2) [42]. Similarly, the conjugation of cetuximab with 131I-labeled AuNHs was performed to target the EGF receptor-expression on the human lung cancer models. The 131I-labeled immune AuNHs exhibited the specific uptake in tumor cells and demonstrated significant accumulation of radiotracers in the tumor tissue. These radiolabeled NHs revealed a high specificity and sensitivity towards EGFR-expressing cells including cancer lung cells. As a result, it was proposed as a promising radiolabeled nanoprobe for the SPECT/CT imaging of the human lung tumors [43]. In a study, to provide targeted and radiolabeled NH for the SPECT/CT imaging, AuNPs were conjugated with the cyclic Arg Gly Asp (cRGD) and labeled with iodine-125 for the in vivo tracking of NHs as the nanoprobe. The SPECT/CT imaging of 125I cRGD AuNHs revealed substantial uptake of these NHs in the tumor cells/tissues, which indicates that they can serve for targeted imaging and radiotherapy of cancer [14]. The preclinical studies for tracking of RGD-modified 111In-labeled AuNHs were developed for target-guided imaging of αvβ3 integrin in the glioblastoma and melanoma models. The in vivo studies and SPECT/CT imaging demonstrated the notable uptake of RGD-modified AuNHs in integrin-expressing tumors. As a result, the NH was suggested for the targetguided detection of the integrin-expressing cancer cells/tissues [44].
II. APPLICATIONS
25.4 RADIOLABELED HYBRID MNPs
541
25.4 RADIOLABELED HYBRID MNPs 25.4.1 Radiolabeled Hybrid MNPs for PET Imaging Radiolabeled hybrid MNPs have also been used in PET imaging. Peripheral artery disease (PAD) is a disease in which narrowed arteries can reduce the blood flow to the limbs that may indicate ischemia in the tissues/organs. Recently, 64Cu-labeled MNPs were developed for the visualization of the ischemic tissues of hindlimb ischemia models. In this study, the PEGylated composite of reduced graphene oxide (rGO)-MNPs was radiolabeled with 64Cu to serve for the photoacoustic (PA) and PET imaging and also benefited from the passive-targeting capabilities of MNPs through EPR effect. The significant localization of 64Cu rGO-MNPs in the ischemic tissue were determined by PET imaging that indicated the potential of these radiolabeled magnetic nanohybrids (MNHs) for PA/PET dual imaging [45]. In another study, the silica-coated MNHs were engineered and labeled with 64Cu. The potential of this nanotracer was evaluated for the PET/MR imaging of cancer cells/tissues. Optimal in vivo accumulation of radiolabeled MNHs in organs and significant stability in serum substantially proved their usefulness for the PET/MR imaging of cancers [46]. In an interesting study, the PEGylated manganese oxide NPs were conjugated with anti-CD105 antibody, TRC105, and further labeled with 64Cu. The examination of the NHs in the 4T1 breast cancer model by PET/MR imaging revealed great PET/MR imaging specificity and sensitivity in terms of breast cancer detection [47]. Furthermore, solid tumors form irregular vasculature through angiogenesis. Tumor microvasculature (TMV) is a pathological process which favors the solid tumors’ progression and invasion. A number of TMV-based molecular markers can be targeted. Angiogenesis can also occur in plaque vulnerability and hemorrhage. Several peptide receptors have been considered as molecular targets for the early detection of angiogenesis using radiolabeled systems. For example, a nine-amino acid cyclic peptide (CTKNSYLMC, GEBP11) was shown to target the neovascularization of endothelial cells. To use its targeting capacity, a dual-modality imaging nanoprobe has recently been engineered by conjugating 2,3-dimercaptosuccinnic acid (DMSA)-coated MNPs (DMSA-MNPs) and 68Ga chelator 1,4,7-triazacyclononane-N,N’,N”-triacetic acid (NOTA) to the GEBP11 peptide (68Ga-NOTA GEBP11 DMSA-MNPs). The 68Ga-NOTA GEBP11 DMSA-MNPs nanoprobe was examined for the dual-modality PET/MR imaging of angiogenesis in the atherosclerosis models. The affinity of peptide was investigated by Prussian blue and immunofluorescence staining. As shown in Fig. 25.3, the findings of this study indicated that the 68Ga-MNHs could serve as a promising PET/MR imaging nanoprobe for the visualization of the vulnerable plaques [48]. The Gallium-68 labeled MNHs were shown to be selectively accumulated in the plaque vasculature, and hence, the NH was proposed as a suitable nanoprobe for in vivo molecular imaging of progressive plaque angiogenesis through dual-modality PET/MR imaging. Similar approaches using MNHs have also been introduced for molecular imaging of malignancies [49]. To develop the dual modality NHs for PET/MRI imaging, Chakravarty et al. reported on the fabrication of the PEGylated 69Ge-SPIONs as one of the biocompatible and safe imaging NHs used for the detection of sentinel lymph nodes. The cellular uptake and
II. APPLICATIONS
542
25. RADIOLABELED THERANOSTICS: MAGNETIC AND GOLD HYBRID NANOPARTICLES
FIGURE 25.3
Nanohybrid for PET imaging. (A) Schematic representation of the production and structure of Ga-NOTA GEBP11 DMSA-MNPs (68Ga-NGD-MNPs). (B) The micro-PET images of 68Ga-NGD-MNPs and 68 Ga-NUD-MNPs on rabbits 2 h after injection. (C) The 68Ga-NGD-MNPs group exhibited significantly more plaque uptake than control group. Source: Image was adapted with permission from a study published by T. Su, Y.B. Wang, D. Han, et al., Multimodality imaging of angiogenesis in a rabbit atherosclerotic model by GEBP11 peptide targeted nanoparticles, Theranostics 7 (2017) 4791 804. 68
biocompatibility of the engineered NHs were evaluated in tumor models. The 69 Ge-labeled NHs showed a substantial stability in the serum and a time-dependent accumulation in tumors, indicating its potential as a multifunctional PET/MR imaging nanoprobe [50].
25.4.2 Radiolabeled Hybrid MNPs for SPECT Imaging MNPs armed with various homing devices and γ-emitting radionuclides can serve for the simultaneous target-guided SPECT imaging and treatment of cells/tissues. Further, acquiring the nuclear and MR imaging using a single dose of contrast agent is one of the significant challenges in the diagnosis of the different diseases/cancers. In a study,
II. APPLICATIONS
25.5 RADIOLABELED Au Fe3O4 HYBRID NANOPARTICLES
543
125
I-labeled magnetoferritin nanocages (M-HFn) NHs were engineered to serve for the imaging of cancerous cells/tissues. The radiolabeled M-HFn nanoprobes were shown to be robustly internalized through a tumor-specific H-ferritin (HFn)-transferrin receptor 1 (TfR1) pathway. These 125I-conjugated M-HFn nanoprobes were shown to provide simultaneous morphological and functional tumor detection by a single dose injection via SPECT/MR imaging [51]. The SPION-based theranostic nanohybrids employed for the diagnosis and targeted α-particle therapy offer a great opportunity for the simultaneous multimodality imaging and treatment of diseases, including different types of tumors. The in vitro results of an investigation indicated that 223Ra-labeled Fe3O4 NPs can be considered as a potential nanoprobe for the theranostic applications [52]. In one study, the PEGylated silica-coated MNPs were functionalized with rituximab and radiolabeled with Rhenium-188 (188Re) as a therapeutic radionuclide for the imaging targeted therapy of cancer cells/tissues. The theranostic efficiency of these NHs was investigated with in vitro and in vivo models, results of which highlighted the promising potential and perspectives of the NHs for the targeted cancer diagnosis/therapy [53]. Lee et al. developed the dextran-coated SPIONs, which were conjugated with technetium-99m (99mTc) as dual modality diagnosis nanoprobe for the SPECT/MR imaging in the liver cancer models. Preclinical studies confirmed the significant uptake of the engineered radiotracer in the cells/tumor sites, and hence nominated them as 99mTc-labeled nanoprobes for the target-guided detection of the hepatic cancers [54]. In a study, the magnetic polymeric NHs were developed via loading of SPIONs into the PEGylated poly(lactic-co-glycolic acid) (PLGA) NPs. Following the labeling of polymeric MNHs using indocyanine green (ICG) and indium-111, the MNHs were examined as multimodal imaging (fluorescence/nuclear imaging/magnetic resonance) nanoprobe on the colon cancer models. Upon the in vitro and in vivo SPECT/CT, optical imaging, and MRI findings, it seems that this polymeric MNH as a multimodal targetguided nanoprobe can be translated into clinical applications for diagnosis of cancers such as colon cancer [55]. Currently, development of the NP-based vaccines to treat and prevent emerging new pathogens, cancers, and infections remain as one of the most challenging issues in the field of biomedicine [56]. In one study, lipid-coated 67Ga-labeled magnetic hybrids were developed for the SPECT/CT tracking of 67Ga-labeled vaccine to the antigen presenting cells. Some preclinical studies have emphasized the potential targeted lymphatic delivery of the radiolabeled nanovaccines to the lymph nodes. All these findings provide compelling evidence that the MNHs can serve as a theranostic vaccine for image-guided applications [57].
25.5 RADIOLABELED Au Fe3O4 HYBRID NANOPARTICLES In order to improve the accuracy of diagnosis and targeted therapy, the multimodal imaging systems are required [58 60]. Having both AuNPs and MNPs within one nanostructure could offer great capability for multimodal target-guided imaging. Yang et al. developed the gold iron oxide heteronanostructures for tumor PET, optical and MR imaging [59]. The authors reported the use of 4 8 nm Au Fe3O4 dumbbell-like nanoparticles
II. APPLICATIONS
544
25. RADIOLABELED THERANOSTICS: MAGNETIC AND GOLD HYBRID NANOPARTICLES
as PET/Optical/MRI probes for cancer imaging in small living animals. Their findings demonstrated that Au Fe3O4 hybrid nanoparticles were the promising nanoplatform for multimodality imaging. Similarly, Zhao et al. reported the use of strawberry-like Fe3O4 Au nanoparticles as CT-MR dual-modality contrast agents for detection of the progressive liver disease [60]. In their study, the in vitro phantom experiment indicated that their hybrid nanoparticles had the superior contrast enhancement for both CT and MR imaging, thus significantly increasing the accuracy of disease detection. Li et al. also synthesized the AuNPs (3.5 nm) decorated Fe3O4 NPs (16.7 nm) for dual-mode MR/CT imaging applications [61]. In case of Fe3O4 Au core shell hybrid nanoparticles, with inner Fe3O4 NP core as an MRI agent, their applications for targeting and multimodal imaging were reported [58,62]. Zhou et al. found that these core shell NPs not only enhanced MR contrast but also were the multimodal contrast probe for both microwave-induced thermoacoustic imaging and photoacoustic imaging [62]. Similarity, Li et al. fabricated the gold-coated Fe3O4 nanoroses with five different functions, such as integrating aptamer-based targeting, MRI, optical imaging, photothermal therapy, and chemotherapy [58].
25.6 CONCLUSION Development of the target-guided radiolabeled NHs to serve as contrast agents for the diagnosis and therapy of diseases such as various malignancies is an ongoing challenge among a large number of scientists. Indeed, simultaneous active targeting and multimodality imaging of defects within the diseased cells/tissues needs implementation of targetguided NHs as contrast agents to be combined with the imaging techniques such as SPECT, PET, MRI, and CT and the integrated imaging techniques. The implementation of radiolabeled target-guided NHs as contrast agent provide key molecular imaging information—important for diagnosis and prognosis of various diseases, including different types of cancers. If coupled with a therapeutic agent, the NHs can be also used as image-guided delivery system for delivery of drug molecules specifically onto the diseased cells/tissue. These NHs can be designed in a way to be responsive to the internal/external stimuli for an on-demand release of drugs. Regarding the AuNPs and Fe3O4 NPs, their hybridization offers great capability for multimodal target-guided imaging. It can be envisioned that many smart NHs, as personalized nanomedicines/theranostics, will be devised in the near future to serve for the simultaneous detection and therapy of diseases. However, despite some advances in the preclinical diagnosis using RNHs, the development of personalized radiolabeled hybrid nanoprobes remains as a significant challenge.
Acknowledgment The authors like to acknowledge the financial support of the Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences.
II. APPLICATIONS
REFERENCES
545
References [1] M. Fathi, P. Sahandi Zangabad, J. Barar, A. Aghanejad, H. Erfan-Niya, Y. Omidi, Thermo-sensitive chitosan copolymer gold hybrid nanoparticles as a nanocarrier for delivery of erlotinib, Int. J. Biol. Macromol. 106 (2018) 266 276. [2] Z. Bakhtiary, J. Barar, A. Aghanejad, et al., Microparticles containing erlotinib-loaded solid lipid nanoparticles for treatment of non-small cell lung cancer, Drug. Dev. Ind. Pharm. 43 (2017) 1244 1253. [3] A. Jafarizad, A. Aghanejad, M. Sevim, et al., Gold nanoparticles and reduced graphene oxide-gold nanoparticle composite materials as covalent drug delivery systems for breast cancer treatment, Chemistry Select. 2 (2017) 6663 6672. [4] J. Barar, Y. Omidi, Surface modified multifunctional nanomedicines for simultaneous imaging and therapy of cancer, Bioimpacts 4 (2014) 3 14. [5] N. Vahidfar, R. Jalilian Amir, Y. Fazaeli, et al., Development of radiolanthanide labeled porphyrin complexes as possible therapeutic agents in beast carcinoma xenografts, Radiochimica Acta 102 (2014) 659 668. [6] A. Aghanejad, A.R. Jalilian, K. Ardaneh, F. Bolourinovin, H. Yousefnia, A.B. Samani, Preparation and quality control of (68)Ga-citrate for PET applications, Asia Ocean J. Nucl. Med. Biol. 3 (2015) 99 106. [7] S. Same, A. Aghanejad, S. Akbari Nakhjavani, J. Barar, Y. Omidi, Radiolabeled theranostics: magnetic and gold nanoparticles, Bioimpacts 6 (2016) 169 181. [8] D. Kryza, J. Taleb, M. Janier, et al., Biodistribution study of nanometric hybrid gadolinium oxide particles as a multimodal SPECT/MR/optical imaging and theragnostic agent, Bioconjug. Chem. 22 (2011) 1145 1152. [9] E.D. Pressly, R.A. Pierce, L.A. Connal, C.J. Hawker, Y. Liu, Nanoparticle PET/CT imaging of natriuretic peptide clearance receptor in prostate cancer, Bioconjug. Chem. 24 (2013) 196 204. [10] S. Liu, B. Jia, R. Qiao, et al., A novel type of dual-modality molecular probe for MR and nuclear imaging of tumor: preparation, characterization and in vivo application, Mol. Pharm. 6 (2009) 1074 1082. [11] I. Tsiapa, E.K. Efthimiadou, E. Fragogeorgi, et al., 99mTc-labeled aminosilane-coated iron oxide nanoparticles for molecular imaging of αvβ3-mediated tumor expression and feasibility for hyperthermia treatment, J. Colloid Interface Sci. 433 (2014) 163 175. [12] L. Karmani, D. Labar, V. Valembois, et al., Antibody-functionalized nanoparticles for imaging cancer: influence of conjugation to gold nanoparticles on the biodistribution of 89Zr-labeled cetuximab in mice, Contrast Media Mol. Imaging 8 (2013) 402 408. [13] B.E. Ocampo-Garcia, M. Ramirez Fde, G. Ferro-Flores, et al., 99mTc-labelled gold nanoparticles capped with HYNIC-peptide/mannose for sentinel lymph node detection, Nucl. Med. Biol. 38 (2011) 1 11. [14] N. Su, Y. Dang, G. Liang, G. Liu, Iodine-125-labeled cRGD gold nanoparticles as tumor-targeted radiosensitizer and imaging agent, Nanoscale Res. Lett. 10 (2015) 160. [15] A. Mirzaei, A.R. Jalilian, A. Aghanejad, et al., Preparation and evaluation of 68Ga-ECC as a PET renal imaging agent, Nucl. Med. Mol. Imaging 49 (2015) 208 216. [16] A. Aghanejad, A.R. Jalilian, S. Maus, H. Yousefnia, P. Geramifar, D. Beiki, Optimized production and quality control of 68Ga-DOTATATE, Iran. J. Nucl. Med. 24 (2016) 29 36. [17] S. Basu, A. Alavi, PET-based personalized management in clinical oncology: an unavoidable path for the foreseeable future, PET Clin. 11 (2016) 203 207. [18] D. Zeng, N.S. Lee, Y. Liu, et al., 64Cu core-labeled nanoparticles with high specific activity via metal-free click chemistry, ACS Nano 6 (2012) 5209 5219. [19] A. Aghanejad, A.R. Jalilian, Y. Fazaeli, et al., Synthesis and evaluation of [67Ga]-AMD3100: a novel imaging agent for targeting the chemokine receptor CXCR4, Sci. Pharm. 82 (2014) 29 42. [20] A. Aghanejad, A.R. Jalilian, Y. Fazaeli, D. Beiki, B. Fateh, A. Khalaj, Radiosynthesis and biodistribution studies of [62Zn/62Cu] plerixafor complex as a novel in vivo PET generator for chemokine receptor imaging, J. Radioanal. Nucl. Chem. 299 (2014) 1635 1644. [21] M. Silindir, S. Erdogan, A.Y. Ozer, et al., Nanosized multifunctional liposomes for tumor diagnosis and molecular imaging by SPECT/CT, J. Liposome Res. 23 (2013) 20 27. [22] J. Garcia, T. Tang, A.Y. Louie, Nanoparticle-based multimodal PET/MRI probes, Nanomedicine (Lond). 10 (2015) 1343 1359. [23] D. Vecchione, M. Aiello, C. Cavaliere, E. Nicolai, P.A. Netti, E. Torino, Hybrid core shell nanoparticles entrapping Gd-DTPA and 18F-FDG for simultaneous PET/MRI acquisitions, Nanomedicine (Lond). 12 (2017) 2223 2231.
II. APPLICATIONS
546
25. RADIOLABELED THERANOSTICS: MAGNETIC AND GOLD HYBRID NANOPARTICLES
[24] A. Abdukayum, C.X. Yang, Q. Zhao, J.T. Chen, L.X. Dong, X.P. Yan, Gadolinium complexes functionalized persistent luminescent nanoparticles as a multimodal probe for near-infrared luminescence and magnetic resonance imaging in vivo, Anal. Chem. 86 (2014) 4096 4101. [25] S.K. Sun, L.X. Dong, Y. Cao, H.R. Sun, X.P. Yan, Fabrication of multifunctional Gd2O3/Au hybrid nanoprobe via a one-step approach for near-infrared fluorescence and magnetic resonance multimodal imaging in vivo, Anal. Chem. 85 (2013) 8436 8441. [26] A. Samarin, F.P. Kuhn, F. Brandsberg, G. von Schulthess, I.A. Burger, Image registration accuracy of an inhouse developed patient transport system for PET/CT 1 MR and SPECT 1 CT imaging, Nucl. Med. Commun. 36 (2015) 194 200. [27] R. Abgral, M.R. Dweck, M.G. Trivieri, et al., Clinical utility of combined FDG-PET/MR to assess myocardial disease, JACC Cardiovasc. Imaging 10 (2017) 594 597. [28] J.R. Lamb, J.P. Holland, Advanced methods for radiolabelling nanomedicines for multi-modality nuclear/ MR imaging, J. Nucl. Med. 59 (2018) 382 389. [29] A. Kumar, S. Zhang, G. Hao, et al., Molecular platform for design and synthesis of targeted dual-modality imaging probes, Bioconjug. Chem. 26 (2015) 549 558. [30] J. Pellico, J. Ruiz-Cabello, M. Saiz-Alia, et al., Fast synthesis and bioconjugation of 68Ga core-doped extremely small iron oxide nanoparticles for PET/MR imaging, Contrast Media Mol. Imaging 11 (2016) 203 210. [31] J. Koziorowski, A.E. Stanciu, V. Gomez-Vallejo, J. Llop, Radiolabeled nanoparticles for cancer diagnosis and therapy, Anticancer Agents Med. Chem. 17 (2017) 333 354. [32] Y. Qian, M. Qiu, Q. Wu, et al., Enhanced cytotoxic activity of cetuximab in EGFR-positive lung cancer by conjugating with gold nanoparticles, Sci. Rep. 4 (2014). Article number 7490, 8 pages. [33] S.B. Lee, S.B. Ahn, S.-W. Lee, et al., Radionuclide-embedded gold nanoparticles for enhanced dendritic cellbased cancer immunotherapy, sensitive and quantitative tracking of dendritic cells with PET and Cerenkov luminescence, NPG Asia Mater. 8 (2016) e281. [34] Y. Zhao, L. Detering, D. Sultan, et al., Gold nanoclusters doped with 64Cu for CXCR4 positron emission tomography imaging of breast cancer and metastasis, ACS Nano 10 (2016) 5959 5970. [35] M.A. Wall, T.M. Shaffer, S. Harmsen, et al., Chelator-free radiolabeling of SERRS nanoparticles for wholebody PET and intraoperative Raman imaging, Theranostics 7 (2017) 3068 3077. [36] P. Bhatnagar, Z. Li, Y. Choi, et al., Imaging of genetically engineered T cells by PET using gold nanoparticles complexed to Copper-64, Integr Biol (Camb). 5 (2013) 231 238. [37] C. Tsoukalas, G. Laurent, G. Jimenez Sanchez, et al., Initial in vitro and in vivo assessment of Au@DTDTPARGD nanoparticles for Gd-MRI and 68Ga-PET dual modality imaging, EJNMMI Phys. 2 (2015) A89. [38] M. Tian, W. Lu, R. Zhang, et al., Tumor uptake of hollow gold nanospheres after intravenous and intraarterial injection: PET/CT study in a rabbit VX2 liver cancer model, Mol. Imaging Biol. 15 (2013) 614 624. [39] X. Li, C. Wang, H. Tan, et al., Gold nanoparticles-based SPECT/CT imaging probe targeting for vulnerable atherosclerosis plaques, Biomaterials 108 (2016) 71 80. [40] F. Silva, A. Zambre, M.P. Campello, et al., Interrogating the role of receptor-mediated mechanisms: biological fate of peptide-functionalized radiolabeled gold nanoparticles in tumor mice, Bioconjug. Chem. 27 (2016) 1153 1164. [41] R. Clanton, A. Gonzalez, S. Shankar, G. Akabani, Rapid synthesis of 125I integrated gold nanoparticles for use in combined neoplasm imaging and targeted radionuclide therapy, Appl. Radiat. Isot. 131 (2018) 49 57. [42] L. Song, S. Able, E. Johnson, K.A. Vallis, Accumulation of 111In-labelled EGF-Au-PEG nanoparticles in EGFRpositive tumours is enhanced by coadministration of targeting ligand, Nanotheranostics 1 (2017) 232 243. [43] H.W. Kao, Y.Y. Lin, C.C. Chen, et al., Evaluation of EGFR-targeted radioimmuno-gold-nanoparticles as a theranostic agent in a tumor animal model, Bioorg. Med. Chem. Lett. 23 (2013) 3180 3185. [44] Q.K. Ng, C.I. Olariu, M. Yaffee, et al., Indium-111 labeled gold nanoparticles for in-vivo molecular targeting, Biomaterials 35 (2014) 7050 7057. [45] C.G. England, H.J. Im, L. Feng, et al., Re-assessing the enhanced permeability and retention effect in peripheral arterial disease using radiolabeled long circulating nanoparticles, Biomaterials 100 (2016) 101 109. [46] J.A. Barreto, M. Matterna, B. Graham, H. Stephan, L. Spiccia, Synthesis, colloidal stability and 64Cu labeling of iron oxide nanoparticles bearing different macrocyclic ligands, New Journal of Chemistry 35 (2011) 2705 2712. [47] Y. Zhan, S. Shi, E.B. Ehlerding, et al., Radiolabeled, antibody-conjugated manganese oxide nanoparticles for tumor vasculature targeted positron emission tomography and magnetic resonance imaging, ACS Appl Mater Interfaces 9 (2017) 38304 38312.
II. APPLICATIONS
REFERENCES
547
[48] T. Su, Y.B. Wang, D. Han, et al., Multimodality imaging of angiogenesis in a rabbit atherosclerotic model by GEBP11 peptide targeted nanoparticles, Theranostics 7 (2017) 4791 4804. [49] M.-A. Karageorgou, S. Vranjeˇs, et al. Gallium-68 labeled iron oxide nanoparticles coated with 2,3-dicarboxypropane-1,1-diphosphonic acid as a potential PET/MR imaging agent: A proof-of-concept study. Contrast Media Mol. Imaging 2017 (2017) Article ID 6951240, 13 pages. [50] R. Chakravarty, H.F. Valdovinos, F. Chen, et al., Intrinsically germanium-69-labeled iron oxide nanoparticles: synthesis and in-vivo dual-modality PET/MR imaging, Adv Mater. 26 (2014) 5119 5123. [51] Y. Zhao, M. Liang, X. Li, et al., Bioengineered magnetoferritin nanoprobes for single-dose nuclear-magnetic resonance tumor imaging, ACS Nano 10 (2016) 4184 4191. [52] O. Mokhodoeva, M. Vlk, E. Ma´lkova´, et al., Study of 223Ra uptake mechanism by Fe3O4 nanoparticles: towards new prospective theranostic SPIONs, J. Nanopart. Res. 18 (2016) 301. [53] B. Azadbakht, H. Afarideh, M. Ghannadi-Maragheh, A. Bahrami-Samani, M. Asgari, Preparation and evaluation of APTES-PEG coated iron oxide nanoparticles conjugated to rhenium-188 labeled rituximab, Nucl. Med. Biol. 48 (2017) 26 30. [54] I.J. Lee, J.Y. Park, Y.I. Kim, et al., Image-based analysis of tumor localization after intra-arterial delivery of technetium-99m-labeled SPIO using SPECT/CT and MRI, Mol. Imaging 16 (2017). 1536012116689001. [55] J. Bai, J.T. Wang, N. Rubio, et al., Triple-modal imaging of magnetically-targeted nanocapsules in solid tumours in vivo, Theranostics 6 (2016) 342 356. [56] M.M. Pourseif, G. Moghaddam, N. Saeedi, A. Barzegari, J. Dehghani, Y. Omidi, Current status and future prospective of vaccine development against Echinococcus granulosus, Biologicals 51 (2018) 1 11. [57] A. Ruiz-de-Angulo, A. Zabaleta, V. Gomez-Vallejo, J. Llop, J.C. Mareque-Rivas, Microdosed lipid-coated 67 Ga-magnetite enhances antigen-specific immunity by image tracked delivery of antigen and CpG to lymph nodes, ACS Nano 10 (2016) 1602 1618. [58] C. Li, T. Chen, I. Ocsoy, G. Zhu, E. Yasun, M. You, et al., Gold-coated Fe3O4 nanoroses with five unique functions for cancer cell targeting, imaging, and therapy, Adv. Funct. Mater. 24 (12) (2014) 1772 1780. [59] M. Yang, K. Cheng, S. Qi, H. Liu, Y. Jiang, H. Jiang, et al., Affibody modified and radiolabeled gold Iron oxide heteronanostructures for tumor PET, optical and MR imaging, Biomaterials 34 (2013) 2796 2806. [60] H.Y. Zhao, S. Liu, J. He, C.C. Pan, H. Li, Z.Y. Zhou, et al., Synthesis and application of strawberry-like Fe3O4 Au nanoparticles as CT-MR dual-modality contrast agents in accurate detection of the progressive liver disease, Biomaterials 51 (2015) 194 207. [61] J. Li, L. Zheng, H. Cai, W. Sun, M. Shen, G. Zhang, et al., Facile one-pot synthesis of Fe3O4@Au composite nanoparticles for dual-mode MR/CT imaging applications, ACS Appl. Mater. Interfaces 5 (2013) 10357 10366. [62] T. Zhou, B. Wu, D. Xing, Bio-modified Fe3O4 core/Au shell nanoparticles for targeting and multimodal imaging of cancer cells, J. Mater. Chem. 22 (2012) 470 477.
II. APPLICATIONS
25 Radiolabeled Theranostics: Magnetic and Gold Hybrid Nanoparticles Ayuob Aghanejad1 and Yadollah Omidi1,2 1
Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran 2Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
25.1 INTRODUCTION Hybrid nanoparticles (HNPs) composed of a targeting agent such as antibody (Ab) or aptamer (Ap), imaging agent (e.g., radionuclide, fluorophore), and therapeutic agent have been developed as theranostic nanocarriers for targeted detection and therapy. Several types of HNPs (e.g., metal/metal oxide, polymer/metal, metal/graphene, lipid/ polymer, radioisotope/metal, etc.) have extensively been explored for the development of improved drug delivery systems (DDSs) with maximal therapeutic effects and minimal side effects [1 3]. The physicochemical features (e.g., morphology, size, surface area, multivalency, and unique optical characteristics) of various metal-based NPs, in particular, gold NPs (AuNPs) and magnetic NPs (MNPs), have widely been exploited to improve the efficiency of target-guided imaging/therapy molecular probes [4]. Further, so far a number of diagnostic procedures has been used for simultaneous diagnosis and therapy of diseases/malignancies using theranostics. Among them, nuclear imaging approach using radiolabeled tracers has been well-established in medical practice and research for decades [5,6]. Various radiolabeled NPs have been employed as hybrid NSs. Accordingly, a number of potent diagnostic modalities, whose applications depend on the radionuclide’s property, has been used as hybrid NPs in imaging techniques such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET) [7]. Overall, the potential of radioisotope-containing NPs (i.e., radiolabeled HNPs) in the accurate medical imaging procedures make them very valuable diagnostic and therapeutic agents. Moreover, radiolabeled hybrid NPs (RHNPs) provide great
Noble Metal-Metal Oxide Hybrid Nanoparticles DOI: https://doi.org/10.1016/B978-0-12-814134-2.00025-5
535
© 2019 Elsevier Inc. All rights reserved.
536
25. RADIOLABELED THERANOSTICS: MAGNETIC AND GOLD HYBRID NANOPARTICLES
TABLE 25.1 Selected Targeted Nanohybrids for PET and SPECT Imaging Nanohybrid
Radionuclide Half-life
Targeting Agent
Application
Ref.
Magnetic
64
12.70 h
C-type atrial natriuretic factor peptide
PET imaging of prostate cancer cells
[9]
59.49 d
3H11 mAb
SPECT/MR imaging of gastric cancer models
[10]
6.02 h
Cyclic Arg Gly Asp DPhe Lys (cRGDfK) peptide
SPECT/MR imaging of glioblastoma
[11]
78.41 h
Cetuximab
PET imaging of the epidermal cancer
[12]
Tc
6.02 h
GGC peptide
SPECT imaging of lymph node
[13]
I
59.49 d
cRGD peptide
SPECT/CT imaging of small cell lung cancer models
[14]
Cu
125
I
99m
Gold
89
Tc
Zr
99m 125
possibility for whole-body imaging with high quantitative and sensitivity, and hence are considered as one of the most reliable and robust methods for the in vitro and in vivo molecular imaging [8]. Table 25.1 shows some selected radiolabeled nanohybrids used for CT, SPECT, PET, and MR imaging. In fact, development of molecular nanoprobes for the target-guided imagining of biological events in the living body without any disruption at molecular and cellular levels can remarkably be beneficial not only for the detection of disease mechanisms but also for the improvement of targeted therapy of designated cells/tissue, in particular in different types of solid tumors.
25.2 IMAGING MODALITIES Different imaging modalities such as isotopic PET and SPECT imaging, computed tomography (CT), and magnetic resonance imaging (MRI), as well as optical imaging by means of various fluorophores have been employed for the accurate diagnosis of a number of formidable diseases, such as malignancies.
25.2.1 PET and SPECT Imaging Systems Undoubtedly, PET is one of the most valuable quantitative imaging technologies with the great detection ability of abnormalities at the molecular and cellular levels [15,16]. In this molecular imaging system, extremely minimized doses of the radiopharmaceuticals with high specific activity are used to acquire high-resolution images—an imaging process that is considered to be safe to other healthy tissues/organs [17,18]. SPECT is another interesting technique with unique features that can be employed for the imaging of emerging biological phenomena at molecular/cellular levels. In addition,
II. APPLICATIONS
25.3 RADIOLABELED HYBRID AuNPs
537
the progression of malignancy, infections, or inflammations and even the delivery of radiopharmaceuticals have been imaged by SPECT and hybrid imaging techniques such as SPECT/CT [19,20]. Moreover, PET, SPECT, and their hybrid imaging systems (e.g., MRI CT hybrid imaging system) were shown to have significant potential in the simultaneous detection of various biological functions. For the probing of different molecular processes by these imaging systems, NP-based probes have successfully been used for multimodal bioimaging using radioisotopes with different emission energies [21,22].
25.2.2 MRI, CT, and Optical Imaging Systems MRI is a nonionization approach, which spots water molecules in the tissues/organs at a magnetic field. This imaging approach has a significant potential for the detection and status of diseases such as tumor progression and even responses to treatment modalities. So far, a number of contrast agents (e.g., MNPs and hybrid NPs) have been used for the implementation of this powerful diagnostic technique [23]. CT as a diagnostic and costeffective tool has been developed for the X-ray-based monitoring of various diseases including different types of solid tumors. Currently, the most common contrast agents of CT are surprisingly used nonspecifically. They are not able to target the desired cells/tissues specifically, failing to detect cancer biomarkers and biological components. Additionally, different types of optical imaging methods based on hybrid NPs (e.g., nearinfrared, fluorescence, etc.) have been developed for monitoring of the biological events, in large part due to their significant complementary imaging features [24,25]. Hence, to provide images with significantly high specificity and resolution, the multimodal imaging systems which merge functional imaging techniques (e.g., SPECT, PET) with anatomically three-dimensional (3D) modalities (e.g., CT, MRI) can be effectively employed and result in improved imaging in comparison with the single modality operating systems [26,27]. The PET CT/MRI and SPECT CT, as remarkable dual-modality imaging techniques, have been employed to improve the medical applications, particularly in diagnosis and therapy of cancers, providing much more functional information, an enhanced soft-tissue contrast, and a lower radiation exposure [28,29]. Fig. 25.1 represents different imaging techniques and multimodal nanohybrids (NHs) as imaging agents.
25.3 RADIOLABELED HYBRID AuNPs Recently, various types of NHs such as superparamagnetic nanoparticles (SPIONs), quantum dots (QDs), and AuNPs have been developed for targeted molecular detection of tumor cell/organs. The promising potential of NPs for functionalization with various ligands make them unique tools for a target-guided imaging. Different moieties can be conjugated to NPs/NHs, including antibodies (Abs), aptamers (Aps), peptides, nucleic acids, and proteins. Based on these facts, radiolabeled functionalized metal NPs, such as magnetic/gold NPs, as imaging probes play an important role in cancer detection by PET, SPECT, and their combined imaging modalities (e.g., SPECT/MR, PET/MR, SPECT/CT, and PET/CT), resulting in reliable information about the cellular and molecular
II. APPLICATIONS
538
25. RADIOLABELED THERANOSTICS: MAGNETIC AND GOLD HYBRID NANOPARTICLES
FIGURE 25.1 Radiolabeled nanohybrids (NHs) for multimodality in vitro and in vivo targeted imaging of cancer. (A) Schematic representation of a radiolabeled nanohybrid conjugated with targeting agent. (B) Various imaging techniques for the diagnosis of cancer. SPECT: Single-photon emission computed tomography; PET: Positronemission tomography; CT: Computed tomography; MRI: Magnetic resonance imaging.
interactions from increasing the signal to noise ratios in desired organs/cells [30,31]. These RHNPs are able to target the diseased organs/cells and provide comprehensive physiologic data in both in vivo and in vitro for diagnosis and treatment of cancers.
25.3.1 Radiolabeled Hybrid AuNPs for PET Imaging The AuNPs distinctive physicochemical properties (e.g., biocompatibility, large surface area, and high stability and photoacoustic features) make them as significant NHs for biomedical applications. Various gold-based nanostructures have been preclinically investigated for imaging/therapy in the cancer cells/tissue, including nanocages, nanoshells, nanorods, and nanospheres [32]. Biologically, the AuNPs are considered as nontoxic and inert materials, which can be used for passive and/or active targeting of desired cell/ organs. PET imaging by means of radiolabeled AuNPs at the target cell/tissue provides key quantitative molecular/cellular imaging information on the diseases with high sensitivity and efficiency. In one study, PET/CT imaging of dendritic cell (DC) using adenine-rich oligonucleotide conjugated 124I-AuNPs was performed for tracking of the DCs migration towards lymph nodes. The DCs were labeled with radionuclide-grafted AuNps and their antitumor immune responses examined in mice models. Interestingly, the results revealed the mice that immunized with Lewis lung carcinoma (LLC) lysates and labeled DCs exhibited a strong antitumor activity [33]. In another study, the 64Cu-labeled gold nanoclusters (NCs) functionalized with plerixafor (AMD3100) were used for the detection of the CXCR4 upregulation in the lung metastasis and primary tumors in the breast cancer models using PET imaging. These radiopharmaceuticals provided great capability for the specific detection of tumors expressing CXCR4, which were then proposed as a target-specific RHNPs for the early and accurate detection of the breast cancer with lung metastasis [34]. The 68Ga-labeled gold NHs (AnNHs) are the dual-modality PET/surface-enhanced resonance Raman scattering (SERRS) imaging probe that was developed for the imaging of both pre-operative and intraoperative profile of diseased lymph nodes. As a result, these
II. APPLICATIONS
25.3 RADIOLABELED HYBRID AuNPs
539
PET SERRS nanohybrids were proposed for the tracking of lymph node, and hence, imaging of the status of the disease after treatment strategies [35]. In one study, PET/CT imaging by means of 64Cu-labeled PEGylated AuNHs was developed for the tracking of T cells in patients with B-cells’ malignancy. For this purpose, the T cells were modified with a CD19 specific chimeric antigen receptor (CAR) and the firefly luciferase (ffLuc) through electrotransferring of DNA plasmids. As a result, these PEGylated GNP 64Cu were proposed as a target-specific radiolabeled NHs for the detection and immunotherapy of cancer [36]. In another study, the PEGylated AuNPs were conjugated with arginylglycylaspartic acid (RGD) peptide and radiolabeled with 68Ga. The NH was then used as PET/MRI imaging tracer to study the overexpressing integrin αvβ3 receptor in U87MG cancer cells. The NHs showed specific accumulation in the U87MG glioma cells and appear to offer efficient potentials for integrin-related tumor imaging [37]. Similarly, the PEGylated hollow AuNPs were radiolabeled with 64Cu and decorated with cyclic RGD to develop a target-guided PET/CT imaging agent. The engineered NHs were examined for intratumor accumulation on the VX2 tumor-bearing rabbits, resulting in specifically targeting of the integrin αvβ3 expressing tissues/cells [38].
25.3.2 Radiolabeled Hybrid AuNPs for SPECT Imaging To investigate the vulnerability of atherosclerotic plaques, in a study, the technetium99m labeled AuNPs were conjugated with Annexin V and used as targeted dual modality SPECT/CT imaging nanoprobe. The engineered AuNHs were shown to serve as a potential radiopharmaceutical for specific diagnosis of apoptotic macrophages in ApoE knockout mice by means of SPECT/CT system [39]. In another study, to provide SPECT nanotracer, AuNPs were functionalized with bombesin (BBN) peptide and labeled with 67Ga and used for the preclinical studies on prostate tumor-bearing mice. These NHs were reported to be largely taken up by the gastrinreleasing peptide (GRP) receptor-expressing tumor cells. In the prostate tumor-bearing mice, an intraperitoneal administration of the NHs resulted in pancreas uptake due to the GRP receptor-mediated mechanism, while the enhanced permeability and retention (EPR) effect seemed to play the major role in the intravenous administration. Taken together, these NHs were proposed to serve as promising radiotracers for imaging of cancer cells [40]. Auger electron-emission is an effective approach for the diagnosis and therapy of diseases such as malignancies. In a study, the PEGlyted 125I AuNHs were developed to serve as a diagnostic and therapeutic agent for the delivery of radionuclides to the neoplasms. Based on the Auger-electron energies, these NHs showed a great potential for the imaging and therapy of cancer cells [41]. It should be noted that targeted radionuclide therapy of solid tumors provides the delivery of a high dose of radioactivity to target cells/tissues with decreased side effects to the surrounding normal tissues, and is considered as one of the important strategies for the detection and therapy of cancer cells/tissues. In a study, indium-111 (111In)-labeled PEGylated epidermal growth factor (EGF)-armed AuNHs were engineered to serve as a
II. APPLICATIONS
540
25. RADIOLABELED THERANOSTICS: MAGNETIC AND GOLD HYBRID NANOPARTICLES
FIGURE 25.2 The whole-body SPECT images in xenograft mice bearing 231-H2N (H2N) and MDA-MB-468 (468) tumors 72 h after injection of 111In-Au-EGF, 111In-Au-EGF-PEG6000 and 111In-Au-EGF-PEG6000 plus 30 μg or 15 μg of EGF bulking dosages (T: tumor; S: spleen; L: liver; K: kidney; B: bladder). Source: Image was adapted with permission from a published work conducted by L. Song, S. Able, E. Johnson, K.A. Vallis, Accumulation of (1 1 1) Inlabelled EGF-Au-PEG nanoparticles in EGFR-positive tumours is enhanced by coadministration of targeting ligand, Nanotheranostics 1 (2017) 232 243.
potential radiopharmaceutical for the detection of EGFR-positive breast cancer. The in vivo micro-SPECT/CT studies of the engineered nanosystem (NS) showed somewhat liver uptake with limited tumor accumulation, in large part because of the moderate expression of EGFR by the hepatocytes as well as the rapid clearance of NSs through the mononuclear phagocyte system. The coadministration of unlabeled EGF to reduce the liver uptake might enhance the accumulation of the NSs in the tumor sites. As a result, these NHs were proposed as the target-specific radiolabeled NSs for the detection of EGFR-positive cancer (Fig. 25.2) [42]. Similarly, the conjugation of cetuximab with 131I-labeled AuNHs was performed to target the EGF receptor-expression on the human lung cancer models. The 131I-labeled immune AuNHs exhibited the specific uptake in tumor cells and demonstrated significant accumulation of radiotracers in the tumor tissue. These radiolabeled NHs revealed a high specificity and sensitivity towards EGFR-expressing cells including cancer lung cells. As a result, it was proposed as a promising radiolabeled nanoprobe for the SPECT/CT imaging of the human lung tumors [43]. In a study, to provide targeted and radiolabeled NH for the SPECT/CT imaging, AuNPs were conjugated with the cyclic Arg Gly Asp (cRGD) and labeled with iodine-125 for the in vivo tracking of NHs as the nanoprobe. The SPECT/CT imaging of 125I cRGD AuNHs revealed substantial uptake of these NHs in the tumor cells/tissues, which indicates that they can serve for targeted imaging and radiotherapy of cancer [14]. The preclinical studies for tracking of RGD-modified 111In-labeled AuNHs were developed for target-guided imaging of αvβ3 integrin in the glioblastoma and melanoma models. The in vivo studies and SPECT/CT imaging demonstrated the notable uptake of RGD-modified AuNHs in integrin-expressing tumors. As a result, the NH was suggested for the targetguided detection of the integrin-expressing cancer cells/tissues [44].
II. APPLICATIONS
25.4 RADIOLABELED HYBRID MNPs
541
25.4 RADIOLABELED HYBRID MNPs 25.4.1 Radiolabeled Hybrid MNPs for PET Imaging Radiolabeled hybrid MNPs have also been used in PET imaging. Peripheral artery disease (PAD) is a disease in which narrowed arteries can reduce the blood flow to the limbs that may indicate ischemia in the tissues/organs. Recently, 64Cu-labeled MNPs were developed for the visualization of the ischemic tissues of hindlimb ischemia models. In this study, the PEGylated composite of reduced graphene oxide (rGO)-MNPs was radiolabeled with 64Cu to serve for the photoacoustic (PA) and PET imaging and also benefited from the passive-targeting capabilities of MNPs through EPR effect. The significant localization of 64Cu rGO-MNPs in the ischemic tissue were determined by PET imaging that indicated the potential of these radiolabeled magnetic nanohybrids (MNHs) for PA/PET dual imaging [45]. In another study, the silica-coated MNHs were engineered and labeled with 64Cu. The potential of this nanotracer was evaluated for the PET/MR imaging of cancer cells/tissues. Optimal in vivo accumulation of radiolabeled MNHs in organs and significant stability in serum substantially proved their usefulness for the PET/MR imaging of cancers [46]. In an interesting study, the PEGylated manganese oxide NPs were conjugated with anti-CD105 antibody, TRC105, and further labeled with 64Cu. The examination of the NHs in the 4T1 breast cancer model by PET/MR imaging revealed great PET/MR imaging specificity and sensitivity in terms of breast cancer detection [47]. Furthermore, solid tumors form irregular vasculature through angiogenesis. Tumor microvasculature (TMV) is a pathological process which favors the solid tumors’ progression and invasion. A number of TMV-based molecular markers can be targeted. Angiogenesis can also occur in plaque vulnerability and hemorrhage. Several peptide receptors have been considered as molecular targets for the early detection of angiogenesis using radiolabeled systems. For example, a nine-amino acid cyclic peptide (CTKNSYLMC, GEBP11) was shown to target the neovascularization of endothelial cells. To use its targeting capacity, a dual-modality imaging nanoprobe has recently been engineered by conjugating 2,3-dimercaptosuccinnic acid (DMSA)-coated MNPs (DMSA-MNPs) and 68Ga chelator 1,4,7-triazacyclononane-N,N’,N”-triacetic acid (NOTA) to the GEBP11 peptide (68Ga-NOTA GEBP11 DMSA-MNPs). The 68Ga-NOTA GEBP11 DMSA-MNPs nanoprobe was examined for the dual-modality PET/MR imaging of angiogenesis in the atherosclerosis models. The affinity of peptide was investigated by Prussian blue and immunofluorescence staining. As shown in Fig. 25.3, the findings of this study indicated that the 68Ga-MNHs could serve as a promising PET/MR imaging nanoprobe for the visualization of the vulnerable plaques [48]. The Gallium-68 labeled MNHs were shown to be selectively accumulated in the plaque vasculature, and hence, the NH was proposed as a suitable nanoprobe for in vivo molecular imaging of progressive plaque angiogenesis through dual-modality PET/MR imaging. Similar approaches using MNHs have also been introduced for molecular imaging of malignancies [49]. To develop the dual modality NHs for PET/MRI imaging, Chakravarty et al. reported on the fabrication of the PEGylated 69Ge-SPIONs as one of the biocompatible and safe imaging NHs used for the detection of sentinel lymph nodes. The cellular uptake and
II. APPLICATIONS
542
25. RADIOLABELED THERANOSTICS: MAGNETIC AND GOLD HYBRID NANOPARTICLES
FIGURE 25.3
Nanohybrid for PET imaging. (A) Schematic representation of the production and structure of Ga-NOTA GEBP11 DMSA-MNPs (68Ga-NGD-MNPs). (B) The micro-PET images of 68Ga-NGD-MNPs and 68 Ga-NUD-MNPs on rabbits 2 h after injection. (C) The 68Ga-NGD-MNPs group exhibited significantly more plaque uptake than control group. Source: Image was adapted with permission from a study published by T. Su, Y.B. Wang, D. Han, et al., Multimodality imaging of angiogenesis in a rabbit atherosclerotic model by GEBP11 peptide targeted nanoparticles, Theranostics 7 (2017) 4791 804. 68
biocompatibility of the engineered NHs were evaluated in tumor models. The 69 Ge-labeled NHs showed a substantial stability in the serum and a time-dependent accumulation in tumors, indicating its potential as a multifunctional PET/MR imaging nanoprobe [50].
25.4.2 Radiolabeled Hybrid MNPs for SPECT Imaging MNPs armed with various homing devices and γ-emitting radionuclides can serve for the simultaneous target-guided SPECT imaging and treatment of cells/tissues. Further, acquiring the nuclear and MR imaging using a single dose of contrast agent is one of the significant challenges in the diagnosis of the different diseases/cancers. In a study,
II. APPLICATIONS
25.5 RADIOLABELED Au Fe3O4 HYBRID NANOPARTICLES
543
125
I-labeled magnetoferritin nanocages (M-HFn) NHs were engineered to serve for the imaging of cancerous cells/tissues. The radiolabeled M-HFn nanoprobes were shown to be robustly internalized through a tumor-specific H-ferritin (HFn)-transferrin receptor 1 (TfR1) pathway. These 125I-conjugated M-HFn nanoprobes were shown to provide simultaneous morphological and functional tumor detection by a single dose injection via SPECT/MR imaging [51]. The SPION-based theranostic nanohybrids employed for the diagnosis and targeted α-particle therapy offer a great opportunity for the simultaneous multimodality imaging and treatment of diseases, including different types of tumors. The in vitro results of an investigation indicated that 223Ra-labeled Fe3O4 NPs can be considered as a potential nanoprobe for the theranostic applications [52]. In one study, the PEGylated silica-coated MNPs were functionalized with rituximab and radiolabeled with Rhenium-188 (188Re) as a therapeutic radionuclide for the imaging targeted therapy of cancer cells/tissues. The theranostic efficiency of these NHs was investigated with in vitro and in vivo models, results of which highlighted the promising potential and perspectives of the NHs for the targeted cancer diagnosis/therapy [53]. Lee et al. developed the dextran-coated SPIONs, which were conjugated with technetium-99m (99mTc) as dual modality diagnosis nanoprobe for the SPECT/MR imaging in the liver cancer models. Preclinical studies confirmed the significant uptake of the engineered radiotracer in the cells/tumor sites, and hence nominated them as 99mTc-labeled nanoprobes for the target-guided detection of the hepatic cancers [54]. In a study, the magnetic polymeric NHs were developed via loading of SPIONs into the PEGylated poly(lactic-co-glycolic acid) (PLGA) NPs. Following the labeling of polymeric MNHs using indocyanine green (ICG) and indium-111, the MNHs were examined as multimodal imaging (fluorescence/nuclear imaging/magnetic resonance) nanoprobe on the colon cancer models. Upon the in vitro and in vivo SPECT/CT, optical imaging, and MRI findings, it seems that this polymeric MNH as a multimodal targetguided nanoprobe can be translated into clinical applications for diagnosis of cancers such as colon cancer [55]. Currently, development of the NP-based vaccines to treat and prevent emerging new pathogens, cancers, and infections remain as one of the most challenging issues in the field of biomedicine [56]. In one study, lipid-coated 67Ga-labeled magnetic hybrids were developed for the SPECT/CT tracking of 67Ga-labeled vaccine to the antigen presenting cells. Some preclinical studies have emphasized the potential targeted lymphatic delivery of the radiolabeled nanovaccines to the lymph nodes. All these findings provide compelling evidence that the MNHs can serve as a theranostic vaccine for image-guided applications [57].
25.5 RADIOLABELED Au Fe3O4 HYBRID NANOPARTICLES In order to improve the accuracy of diagnosis and targeted therapy, the multimodal imaging systems are required [58 60]. Having both AuNPs and MNPs within one nanostructure could offer great capability for multimodal target-guided imaging. Yang et al. developed the gold iron oxide heteronanostructures for tumor PET, optical and MR imaging [59]. The authors reported the use of 4 8 nm Au Fe3O4 dumbbell-like nanoparticles
II. APPLICATIONS
544
25. RADIOLABELED THERANOSTICS: MAGNETIC AND GOLD HYBRID NANOPARTICLES
as PET/Optical/MRI probes for cancer imaging in small living animals. Their findings demonstrated that Au Fe3O4 hybrid nanoparticles were the promising nanoplatform for multimodality imaging. Similarly, Zhao et al. reported the use of strawberry-like Fe3O4 Au nanoparticles as CT-MR dual-modality contrast agents for detection of the progressive liver disease [60]. In their study, the in vitro phantom experiment indicated that their hybrid nanoparticles had the superior contrast enhancement for both CT and MR imaging, thus significantly increasing the accuracy of disease detection. Li et al. also synthesized the AuNPs (3.5 nm) decorated Fe3O4 NPs (16.7 nm) for dual-mode MR/CT imaging applications [61]. In case of Fe3O4 Au core shell hybrid nanoparticles, with inner Fe3O4 NP core as an MRI agent, their applications for targeting and multimodal imaging were reported [58,62]. Zhou et al. found that these core shell NPs not only enhanced MR contrast but also were the multimodal contrast probe for both microwave-induced thermoacoustic imaging and photoacoustic imaging [62]. Similarity, Li et al. fabricated the gold-coated Fe3O4 nanoroses with five different functions, such as integrating aptamer-based targeting, MRI, optical imaging, photothermal therapy, and chemotherapy [58].
25.6 CONCLUSION Development of the target-guided radiolabeled NHs to serve as contrast agents for the diagnosis and therapy of diseases such as various malignancies is an ongoing challenge among a large number of scientists. Indeed, simultaneous active targeting and multimodality imaging of defects within the diseased cells/tissues needs implementation of targetguided NHs as contrast agents to be combined with the imaging techniques such as SPECT, PET, MRI, and CT and the integrated imaging techniques. The implementation of radiolabeled target-guided NHs as contrast agent provide key molecular imaging information—important for diagnosis and prognosis of various diseases, including different types of cancers. If coupled with a therapeutic agent, the NHs can be also used as image-guided delivery system for delivery of drug molecules specifically onto the diseased cells/tissue. These NHs can be designed in a way to be responsive to the internal/external stimuli for an on-demand release of drugs. Regarding the AuNPs and Fe3O4 NPs, their hybridization offers great capability for multimodal target-guided imaging. It can be envisioned that many smart NHs, as personalized nanomedicines/theranostics, will be devised in the near future to serve for the simultaneous detection and therapy of diseases. However, despite some advances in the preclinical diagnosis using RNHs, the development of personalized radiolabeled hybrid nanoprobes remains as a significant challenge.
Acknowledgment The authors like to acknowledge the financial support of the Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences.
II. APPLICATIONS
REFERENCES
545
References [1] M. Fathi, P. Sahandi Zangabad, J. Barar, A. Aghanejad, H. Erfan-Niya, Y. Omidi, Thermo-sensitive chitosan copolymer gold hybrid nanoparticles as a nanocarrier for delivery of erlotinib, Int. J. Biol. Macromol. 106 (2018) 266 276. [2] Z. Bakhtiary, J. Barar, A. Aghanejad, et al., Microparticles containing erlotinib-loaded solid lipid nanoparticles for treatment of non-small cell lung cancer, Drug. Dev. Ind. Pharm. 43 (2017) 1244 1253. [3] A. Jafarizad, A. Aghanejad, M. Sevim, et al., Gold nanoparticles and reduced graphene oxide-gold nanoparticle composite materials as covalent drug delivery systems for breast cancer treatment, Chemistry Select. 2 (2017) 6663 6672. [4] J. Barar, Y. Omidi, Surface modified multifunctional nanomedicines for simultaneous imaging and therapy of cancer, Bioimpacts 4 (2014) 3 14. [5] N. Vahidfar, R. Jalilian Amir, Y. Fazaeli, et al., Development of radiolanthanide labeled porphyrin complexes as possible therapeutic agents in beast carcinoma xenografts, Radiochimica Acta 102 (2014) 659 668. [6] A. Aghanejad, A.R. Jalilian, K. Ardaneh, F. Bolourinovin, H. Yousefnia, A.B. Samani, Preparation and quality control of (68)Ga-citrate for PET applications, Asia Ocean J. Nucl. Med. Biol. 3 (2015) 99 106. [7] S. Same, A. Aghanejad, S. Akbari Nakhjavani, J. Barar, Y. Omidi, Radiolabeled theranostics: magnetic and gold nanoparticles, Bioimpacts 6 (2016) 169 181. [8] D. Kryza, J. Taleb, M. Janier, et al., Biodistribution study of nanometric hybrid gadolinium oxide particles as a multimodal SPECT/MR/optical imaging and theragnostic agent, Bioconjug. Chem. 22 (2011) 1145 1152. [9] E.D. Pressly, R.A. Pierce, L.A. Connal, C.J. Hawker, Y. Liu, Nanoparticle PET/CT imaging of natriuretic peptide clearance receptor in prostate cancer, Bioconjug. Chem. 24 (2013) 196 204. [10] S. Liu, B. Jia, R. Qiao, et al., A novel type of dual-modality molecular probe for MR and nuclear imaging of tumor: preparation, characterization and in vivo application, Mol. Pharm. 6 (2009) 1074 1082. [11] I. Tsiapa, E.K. Efthimiadou, E. Fragogeorgi, et al., 99mTc-labeled aminosilane-coated iron oxide nanoparticles for molecular imaging of αvβ3-mediated tumor expression and feasibility for hyperthermia treatment, J. Colloid Interface Sci. 433 (2014) 163 175. [12] L. Karmani, D. Labar, V. Valembois, et al., Antibody-functionalized nanoparticles for imaging cancer: influence of conjugation to gold nanoparticles on the biodistribution of 89Zr-labeled cetuximab in mice, Contrast Media Mol. Imaging 8 (2013) 402 408. [13] B.E. Ocampo-Garcia, M. Ramirez Fde, G. Ferro-Flores, et al., 99mTc-labelled gold nanoparticles capped with HYNIC-peptide/mannose for sentinel lymph node detection, Nucl. Med. Biol. 38 (2011) 1 11. [14] N. Su, Y. Dang, G. Liang, G. Liu, Iodine-125-labeled cRGD gold nanoparticles as tumor-targeted radiosensitizer and imaging agent, Nanoscale Res. Lett. 10 (2015) 160. [15] A. Mirzaei, A.R. Jalilian, A. Aghanejad, et al., Preparation and evaluation of 68Ga-ECC as a PET renal imaging agent, Nucl. Med. Mol. Imaging 49 (2015) 208 216. [16] A. Aghanejad, A.R. Jalilian, S. Maus, H. Yousefnia, P. Geramifar, D. Beiki, Optimized production and quality control of 68Ga-DOTATATE, Iran. J. Nucl. Med. 24 (2016) 29 36. [17] S. Basu, A. Alavi, PET-based personalized management in clinical oncology: an unavoidable path for the foreseeable future, PET Clin. 11 (2016) 203 207. [18] D. Zeng, N.S. Lee, Y. Liu, et al., 64Cu core-labeled nanoparticles with high specific activity via metal-free click chemistry, ACS Nano 6 (2012) 5209 5219. [19] A. Aghanejad, A.R. Jalilian, Y. Fazaeli, et al., Synthesis and evaluation of [67Ga]-AMD3100: a novel imaging agent for targeting the chemokine receptor CXCR4, Sci. Pharm. 82 (2014) 29 42. [20] A. Aghanejad, A.R. Jalilian, Y. Fazaeli, D. Beiki, B. Fateh, A. Khalaj, Radiosynthesis and biodistribution studies of [62Zn/62Cu] plerixafor complex as a novel in vivo PET generator for chemokine receptor imaging, J. Radioanal. Nucl. Chem. 299 (2014) 1635 1644. [21] M. Silindir, S. Erdogan, A.Y. Ozer, et al., Nanosized multifunctional liposomes for tumor diagnosis and molecular imaging by SPECT/CT, J. Liposome Res. 23 (2013) 20 27. [22] J. Garcia, T. Tang, A.Y. Louie, Nanoparticle-based multimodal PET/MRI probes, Nanomedicine (Lond). 10 (2015) 1343 1359. [23] D. Vecchione, M. Aiello, C. Cavaliere, E. Nicolai, P.A. Netti, E. Torino, Hybrid core shell nanoparticles entrapping Gd-DTPA and 18F-FDG for simultaneous PET/MRI acquisitions, Nanomedicine (Lond). 12 (2017) 2223 2231.
II. APPLICATIONS
546
25. RADIOLABELED THERANOSTICS: MAGNETIC AND GOLD HYBRID NANOPARTICLES
[24] A. Abdukayum, C.X. Yang, Q. Zhao, J.T. Chen, L.X. Dong, X.P. Yan, Gadolinium complexes functionalized persistent luminescent nanoparticles as a multimodal probe for near-infrared luminescence and magnetic resonance imaging in vivo, Anal. Chem. 86 (2014) 4096 4101. [25] S.K. Sun, L.X. Dong, Y. Cao, H.R. Sun, X.P. Yan, Fabrication of multifunctional Gd2O3/Au hybrid nanoprobe via a one-step approach for near-infrared fluorescence and magnetic resonance multimodal imaging in vivo, Anal. Chem. 85 (2013) 8436 8441. [26] A. Samarin, F.P. Kuhn, F. Brandsberg, G. von Schulthess, I.A. Burger, Image registration accuracy of an inhouse developed patient transport system for PET/CT 1 MR and SPECT 1 CT imaging, Nucl. Med. Commun. 36 (2015) 194 200. [27] R. Abgral, M.R. Dweck, M.G. Trivieri, et al., Clinical utility of combined FDG-PET/MR to assess myocardial disease, JACC Cardiovasc. Imaging 10 (2017) 594 597. [28] J.R. Lamb, J.P. Holland, Advanced methods for radiolabelling nanomedicines for multi-modality nuclear/ MR imaging, J. Nucl. Med. 59 (2018) 382 389. [29] A. Kumar, S. Zhang, G. Hao, et al., Molecular platform for design and synthesis of targeted dual-modality imaging probes, Bioconjug. Chem. 26 (2015) 549 558. [30] J. Pellico, J. Ruiz-Cabello, M. Saiz-Alia, et al., Fast synthesis and bioconjugation of 68Ga core-doped extremely small iron oxide nanoparticles for PET/MR imaging, Contrast Media Mol. Imaging 11 (2016) 203 210. [31] J. Koziorowski, A.E. Stanciu, V. Gomez-Vallejo, J. Llop, Radiolabeled nanoparticles for cancer diagnosis and therapy, Anticancer Agents Med. Chem. 17 (2017) 333 354. [32] Y. Qian, M. Qiu, Q. Wu, et al., Enhanced cytotoxic activity of cetuximab in EGFR-positive lung cancer by conjugating with gold nanoparticles, Sci. Rep. 4 (2014). Article number 7490, 8 pages. [33] S.B. Lee, S.B. Ahn, S.-W. Lee, et al., Radionuclide-embedded gold nanoparticles for enhanced dendritic cellbased cancer immunotherapy, sensitive and quantitative tracking of dendritic cells with PET and Cerenkov luminescence, NPG Asia Mater. 8 (2016) e281. [34] Y. Zhao, L. Detering, D. Sultan, et al., Gold nanoclusters doped with 64Cu for CXCR4 positron emission tomography imaging of breast cancer and metastasis, ACS Nano 10 (2016) 5959 5970. [35] M.A. Wall, T.M. Shaffer, S. Harmsen, et al., Chelator-free radiolabeling of SERRS nanoparticles for wholebody PET and intraoperative Raman imaging, Theranostics 7 (2017) 3068 3077. [36] P. Bhatnagar, Z. Li, Y. Choi, et al., Imaging of genetically engineered T cells by PET using gold nanoparticles complexed to Copper-64, Integr Biol (Camb). 5 (2013) 231 238. [37] C. Tsoukalas, G. Laurent, G. Jimenez Sanchez, et al., Initial in vitro and in vivo assessment of Au@DTDTPARGD nanoparticles for Gd-MRI and 68Ga-PET dual modality imaging, EJNMMI Phys. 2 (2015) A89. [38] M. Tian, W. Lu, R. Zhang, et al., Tumor uptake of hollow gold nanospheres after intravenous and intraarterial injection: PET/CT study in a rabbit VX2 liver cancer model, Mol. Imaging Biol. 15 (2013) 614 624. [39] X. Li, C. Wang, H. Tan, et al., Gold nanoparticles-based SPECT/CT imaging probe targeting for vulnerable atherosclerosis plaques, Biomaterials 108 (2016) 71 80. [40] F. Silva, A. Zambre, M.P. Campello, et al., Interrogating the role of receptor-mediated mechanisms: biological fate of peptide-functionalized radiolabeled gold nanoparticles in tumor mice, Bioconjug. Chem. 27 (2016) 1153 1164. [41] R. Clanton, A. Gonzalez, S. Shankar, G. Akabani, Rapid synthesis of 125I integrated gold nanoparticles for use in combined neoplasm imaging and targeted radionuclide therapy, Appl. Radiat. Isot. 131 (2018) 49 57. [42] L. Song, S. Able, E. Johnson, K.A. Vallis, Accumulation of 111In-labelled EGF-Au-PEG nanoparticles in EGFRpositive tumours is enhanced by coadministration of targeting ligand, Nanotheranostics 1 (2017) 232 243. [43] H.W. Kao, Y.Y. Lin, C.C. Chen, et al., Evaluation of EGFR-targeted radioimmuno-gold-nanoparticles as a theranostic agent in a tumor animal model, Bioorg. Med. Chem. Lett. 23 (2013) 3180 3185. [44] Q.K. Ng, C.I. Olariu, M. Yaffee, et al., Indium-111 labeled gold nanoparticles for in-vivo molecular targeting, Biomaterials 35 (2014) 7050 7057. [45] C.G. England, H.J. Im, L. Feng, et al., Re-assessing the enhanced permeability and retention effect in peripheral arterial disease using radiolabeled long circulating nanoparticles, Biomaterials 100 (2016) 101 109. [46] J.A. Barreto, M. Matterna, B. Graham, H. Stephan, L. Spiccia, Synthesis, colloidal stability and 64Cu labeling of iron oxide nanoparticles bearing different macrocyclic ligands, New Journal of Chemistry 35 (2011) 2705 2712. [47] Y. Zhan, S. Shi, E.B. Ehlerding, et al., Radiolabeled, antibody-conjugated manganese oxide nanoparticles for tumor vasculature targeted positron emission tomography and magnetic resonance imaging, ACS Appl Mater Interfaces 9 (2017) 38304 38312.
II. APPLICATIONS
REFERENCES
547
[48] T. Su, Y.B. Wang, D. Han, et al., Multimodality imaging of angiogenesis in a rabbit atherosclerotic model by GEBP11 peptide targeted nanoparticles, Theranostics 7 (2017) 4791 4804. [49] M.-A. Karageorgou, S. Vranjeˇs, et al. Gallium-68 labeled iron oxide nanoparticles coated with 2,3-dicarboxypropane-1,1-diphosphonic acid as a potential PET/MR imaging agent: A proof-of-concept study. Contrast Media Mol. Imaging 2017 (2017) Article ID 6951240, 13 pages. [50] R. Chakravarty, H.F. Valdovinos, F. Chen, et al., Intrinsically germanium-69-labeled iron oxide nanoparticles: synthesis and in-vivo dual-modality PET/MR imaging, Adv Mater. 26 (2014) 5119 5123. [51] Y. Zhao, M. Liang, X. Li, et al., Bioengineered magnetoferritin nanoprobes for single-dose nuclear-magnetic resonance tumor imaging, ACS Nano 10 (2016) 4184 4191. [52] O. Mokhodoeva, M. Vlk, E. Ma´lkova´, et al., Study of 223Ra uptake mechanism by Fe3O4 nanoparticles: towards new prospective theranostic SPIONs, J. Nanopart. Res. 18 (2016) 301. [53] B. Azadbakht, H. Afarideh, M. Ghannadi-Maragheh, A. Bahrami-Samani, M. Asgari, Preparation and evaluation of APTES-PEG coated iron oxide nanoparticles conjugated to rhenium-188 labeled rituximab, Nucl. Med. Biol. 48 (2017) 26 30. [54] I.J. Lee, J.Y. Park, Y.I. Kim, et al., Image-based analysis of tumor localization after intra-arterial delivery of technetium-99m-labeled SPIO using SPECT/CT and MRI, Mol. Imaging 16 (2017). 1536012116689001. [55] J. Bai, J.T. Wang, N. Rubio, et al., Triple-modal imaging of magnetically-targeted nanocapsules in solid tumours in vivo, Theranostics 6 (2016) 342 356. [56] M.M. Pourseif, G. Moghaddam, N. Saeedi, A. Barzegari, J. Dehghani, Y. Omidi, Current status and future prospective of vaccine development against Echinococcus granulosus, Biologicals 51 (2018) 1 11. [57] A. Ruiz-de-Angulo, A. Zabaleta, V. Gomez-Vallejo, J. Llop, J.C. Mareque-Rivas, Microdosed lipid-coated 67 Ga-magnetite enhances antigen-specific immunity by image tracked delivery of antigen and CpG to lymph nodes, ACS Nano 10 (2016) 1602 1618. [58] C. Li, T. Chen, I. Ocsoy, G. Zhu, E. Yasun, M. You, et al., Gold-coated Fe3O4 nanoroses with five unique functions for cancer cell targeting, imaging, and therapy, Adv. Funct. Mater. 24 (12) (2014) 1772 1780. [59] M. Yang, K. Cheng, S. Qi, H. Liu, Y. Jiang, H. Jiang, et al., Affibody modified and radiolabeled gold Iron oxide heteronanostructures for tumor PET, optical and MR imaging, Biomaterials 34 (2013) 2796 2806. [60] H.Y. Zhao, S. Liu, J. He, C.C. Pan, H. Li, Z.Y. Zhou, et al., Synthesis and application of strawberry-like Fe3O4 Au nanoparticles as CT-MR dual-modality contrast agents in accurate detection of the progressive liver disease, Biomaterials 51 (2015) 194 207. [61] J. Li, L. Zheng, H. Cai, W. Sun, M. Shen, G. Zhang, et al., Facile one-pot synthesis of Fe3O4@Au composite nanoparticles for dual-mode MR/CT imaging applications, ACS Appl. Mater. Interfaces 5 (2013) 10357 10366. [62] T. Zhou, B. Wu, D. Xing, Bio-modified Fe3O4 core/Au shell nanoparticles for targeting and multimodal imaging of cancer cells, J. Mater. Chem. 22 (2012) 470 477.
II. APPLICATIONS