- Email: [email protected]
The preparation of 99mTc-DTPA-LSA and its instant lyophilized kit for hepatic receptor imaging
710
Abstracts / Nuclear Medicine and Biology 37 (2010) 677–726 99m
[1] Maria L, Cunha S, Videira M, Gano L, Paulo A, Santos IC, et al. Dalton Trans 2007:3010-9. [2] Maria L, Fernandes C, Garcia R, Gano L, Paulo A, Santos IC, et al. Dalton Trans 2009:603-6.
olabeled peptides were evaluated in SCID female mice bearing human MDA-MB-435 breast tumors. Results: 99mTc(CO)3-DAP-GSG-KCCYSL and 99mTc(CO)3-(NαHis)AcGSG-KCCYSL were stable and bound to ErbB-2-expressing MDA-MB-435 cells. In vivo biodistribution studies revealed that tumor uptake of 99m Tc(CO)3-DAP-GSG-KCCYSL was 1.67±0.16, 1.25±0.61, 0.88±0.12, 0.30±0.06 %ID/g at 1, 2, 4, and 24 post injection, respectively. Tumor uptake of 99m Tc(CO) 3 -(NαHis)Ac-GSG-KCCYSL was 0.76±0.13, 0.75±0.40, 0.33±0.08, 0.16±0.02 %ID/g at 1, 2, 4, and 24 post injection, respectively. SPECT/computed tomographic studies showed tumor selective uptake of both the peptides in the tumor-bearing mice. Specific uptake was confirmed by competitive receptor blocking studies. Conclusions: 99mTc(CO)3-DAP-GSG-KCCYSL and 99mTc(CO)3-(NαHis) Ac-GSG-KCCYSL have the potential to be used as tumor imaging probes. Research Support: National Institutes of Health 1R-21CA137239-01A1 and a Merit Review Award from the Veterans Administration.
doi:10.1016/j.nucmedbio.2010.04.103
doi:10.1016/j.nucmedbio.2010.04.136
ethanamine and tris(pyrazolyl)methane Tc-tricarbonyl complexes (1a– 5a) were synthesized and its potential interest for tumor detection evaluated in human cancer cell lines of different etiology. Herein, we will present the in vitro uptake and efflux kinetic studies undertaken and the results will be compared with those obtained for 99mTc-Sestamibi and 99mTc-Tetrofosmin. For the complexes presenting internalization rates and retention in tumor cells higher than found for 99mTc-Sestamibi, the uptake mechanism in tumor cells was also studied and will be presented and discussed in this communication. References
Correlation between GC-C expression and uptake of GC-C-targeted imaging agents in vitro and in vivo
Trifunctional tricarbonyl complexes for cell-specific and nuclear targeting
Dijie Liu a,d, Leonard R. Forte c, Michael F. Giblin a,b,d,⁎ a Harry S. Truman Memorial Veterans Administration Hospital b Department of Radiology, University of Missouri-Columbia c Department of Medical Pharmacology and Physiology, University of Missouri-Columbia d Radiopharmaceutical Sciences Institute, University of Missouri-Columbia
Teresa Esteves a, Fernanda Marques a, José Rino b, António Paulo a, Charles J. Smith c, Isabel Santos a a UCQR, ITN, Sacavém, Portugal b IMM, FMUL, Lisboa, Portugal c Department Radiology and HSTMVH, Missouri, USA
The guanylyl cyclase C (GC-C) receptor is currently under investigation as a specific biomarker for metastatic colorectal cancer. Agonist activation of GC-C results in initiation of a signaling cascade that ultimately results in inhibition of proliferation of GC-C-expressing cells. The pharmacological use of GC-C agonists is therefore receiving increasing attention as a new paradigm for the treatment of colorectal cancer. In this study, we have correlated GC-C expression in three colorectal cancer cell lines with uptake of molecular imaging agents targeting GC-C in vitro and in vivo. Receptor expression in these three cell lines differs across a wide range (T84NLS174T≫HT-29), as determined by western blot and receptor binding assay. In vivo, tumor uptake of 111In-labeled GC-C agonists was found to vary according to receptor expression at both 1 and 4 hr pi. Molecular imaging with GC-C-specific radiopharmaceuticals could provide a practical method of selection of subpopulations of individuals who may benefit from treatment with GC-C-targeted therapeutic agents. doi:10.1016/j.nucmedbio.2010.04.149 Evaluation of [99mTc(CO)3]-labeled ErbB-2-targeting peptides for breast carcinoma imaging Susan L. Deutscher Department of Biochemistry, University of Missouri and Research Service, Harry S. Truman Veterans Memorial Hospital, Columbia, MO, USA Objectives: The purpose of this study was to radiolabel a novel ErbB-2-avid peptide, discovered from bacteriophage display, with [99mTc(H2O)3(CO)3]+ and evaluate the in vitro cellular targeting and in vivo tumor imaging properties of the peptide in a mouse model of human breast cancer. Methods: The peptide, KCCYSL, synthesized with the chelates diaminopropionc acid (DAP) or Nα-histidinyl acetic acid [(NαHis)Ac] at its aminoterminus, was radiolabeled with [99mTc(H2O)3(CO)3]+. The radiochemical stabilities of the peptides were assessed and in vitro binding to MDA-MB435 human breast carcinoma cells was analyzed. Biodistributions and single photon emission computed tomographic (SPECT) imaging of the radi-
Novel structures labeled with Auger emitters, such as 99mTc, with high affinity for receptors expressed on tumor cells and directed at the nucleus of those cells may have therapeutic potential. Additionally, the introduction of a DNA-binding and/or fluorescent groups in the same molecule may improve the therapeutic effect and will allow to follow the trafficking and fate of the compounds at the cellular and subcellular level. Alberto et al., pioneered the design of Re and Tc complexes bearing a DNA-binding group that can reach the nucleus of given cells without the need of a nuclear localization signal [1]. Using murine melanoma cells, we have also shown that nuclear targeting and radiotoxicity effects can be achieved with tricarbonyl complexes anchored by pyrazolyl-diamine ligands bearing DNA-binding groups [2,3]. In order to make such compounds cell-specific, trifunctional tricarbonyl complexes bearing fluorescent DNA-intercalators and bombesin analogues have been isolated, characterized and biologically evaluated. Herein, we will report on these novel trifunctional tricarbonyl complexes which are cell-specific and target the nucleus. References [1] Alberto, et al. Chem Eur J 2007;13:3842. [2] Santos, et al. Chem Bio Chem 2008;9:131-42. [3] Santos, et al. Cancer Biother Radiopharm 2009;5:1-13. doi:10.1016/j.nucmedbio.2010.04.065 The preparation of 99mTc-DTPA-LSA and its instant lyophilized kit for hepatic receptor imaging Wenjiang Yang, Xianzhong Zhang⁎, Xuebin Wang, Zhigang Tang Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China Introduction: 99mTc-DTPA-LSA was developed for hepatic receptor imaging. Methods: Neolactosylated human serum albumin (LSA) was prepared by covalent coupling lactose to HSA using reductive amination method. Bifunctional chelator diethylenetriamine pentaacetic acid (DTPA) was
Abstracts / Nuclear Medicine and Biology 37 (2010) 677–726 introduced to LSA via DTPA anhydride. DTPA-LSA was labeled with technetium-99m by using SnCl2 as reductant and labeling conditions of 99mTcDTPA-LSA were optimized. Lyophilized kit of DTPA-LSA was also developed for instant preparing of 99mTc-DTPA-LSA. Results: Technetium labeling yields in excess of 93% by using both of liquid and lyophilized labeling methods. Biodistribution of 99mTc-DTPA-LSA was investigated in both normal and liver-injury model mice. It showed high liver uptake in normal mice (N96%ID·g−1 at 5 min after injection), and it could be blocked significantly by pre-injecting free NGA. The liver uptake of 99mTcDTPA-LSA in liver-injury model mice was lower than that of normal mice (P=.0149). Conclusions: The promising biological properties of 99mTc-DTPA-LSA combined with the development of reliable and instant lyophilized DTPALSA kit afford the opportunity of hepatic receptor imaging for routine clinical assessment of hepatocyte function. The project was sponsored by SRF for ROCS and SEM and supported partially by the Scientific Research Foundation of Beijing Normal University. doi:10.1016/j.nucmedbio.2010.04.008
711
99m
and Tc-HEDP, for bone imaging [1]. Since aminobisphosphonates are very polar drugs with low membrane permeability, new amino acid derivatives have been synthesized in order to improve bioavailability and potency [2,3]. Aiming at the preparation of novel radioactivity delivery systems for target therapy (e.g., 188/186 Re) or diagnostic (99mTc) of bone diseases, herein we describe the synthesis and characterization of new glutamic acid derivatives containing a bisphosphonate unit.
References [1] Fleish H. Bisphosphonates in bone disease. In: Fleish H, editor. From the Laboratory to the Patient. 2nd ed. New York (NY): The Parthenon Publishing Group; 1995. [2] Ezra A, Golomb G. Administration routes and delivery systems of bisphosphonates for the treatment of bone resorption. Adv Drug Del Rev 2000;42:175. [3] Mizrahi DM, Wagner T, Segall Y. α-amino acid derived bisphosphonates. Synthesis and anti-resorptive activity. Phosphorus Sulfur Silicon 2001;173:1.
Synthesis and evaluation of a novel folate derivative labeled with 99mTc
doi:10.1016/j.nucmedbio.2010.04.137
Yan Pang, Hongjuan Guo, Meilin Zhu, Fang Xie, Jie Lu Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education; College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China
Development of 188Re-BMEDA encapsulated PEGylated liposome as a diagnostic and therapeutic agent for glioma
The folate receptor (FR) is over expressed in many human tumor, but present in low in most normal tissues and organs. Therefore, folate derivatives labeled with radionuclides could be used for tumor diagnosis and therapy. In this report, a novel folate-HYNIC conjugate (FA-NHHN-HYNIC) was synthesized and labeled with 99mTc using tricine and 99mTc(HYNIC-NHHN-FA)(Tricine) (TPPTS) as coligands. TPPTS was purified by high-performance liquid chromatography for in vitro/in vivo experiments. This hydrophilic complex was stable both in saline and serum. Cell binding experiments revealed that the complex can be taken and internalized by FR-positive KB tumor cells; meanwhile, the accumulation was blocked with excess folic acid. In vivo biodistribution in athymic nude mice bearing KB tumor cells showed that the complex had high uptakes in FR-positive tumor (9.79±1.66% ID/g, 4 h after injection) and blockade studies confirmed specific accumulation of the radiotracer. The accumulation in other non-targeted tissues and organs were low, tumor-to-blood and tumor-to-muscle ratios reached 35.80±10.05 and 10.55±3.71 at 4 h after injecting, respectively. This complex could be a potent agent for folate receptor imaging. Acknowledgments This work was supported by the National Natural Science Foundation of China (20701004). doi:10.1016/j.nucmedbio.2010.04.003 1-Hydroxybisphosphonate-containing amino acids for radioactivity delivery Elisa Palma, João D.G. Correia, Lurdes Gano, Isabel Santos U.C.Q.R., Instituto Tecnológico e Nuclear, Estrada Nacional 10, 2686-953 Sacavém, Portugal Geminal bisphosphonates are a class of compounds that present very high affinity for the bone mineral matrix because they bind strongly to its main component, the hydroxyapatite crystals. Some bisphosphonates have been approved for clinical use in Paget's disease, hypercalcemia of malignancy and osteoporosis. They are also used in the preparation of 99mTc-radiopharmaceuticals, such as 99mTc-MDP
Feng-Yun Huang a, Te-Wei Leeb, Chih-Hao K. Kaoc, Chih-Hsien Chang b, Wan-Yu Lee a, Way-Yi Chen a, Jem-Mau Lo a a Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan b Institute of Nuclear Energy Research, Longtan, Taiwan c Department of Radiopharmaceutical Production, Tzu Chi General Hospital, Hualien, Taiwan 188
Re-N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA) was encapsulated into the PEGylated liposome to produce the 188ReBMEDA-liposome nanoparticles sized at 85±20 nm in diameter. Radiochemical yield of 188Re-BMEDA-liposome could achieve ≥85%. The agent was administrated into the orthotopic F344/F98 brain glioma tumor bearing animal model via tail vein. Biodistribution study, mirco-single photon emission computed tomography/computed tomographic (SPECT/ CT) imaging, autoradiography and hematoxylin and eosin (H&E) staining were carried out at varying postinjection time points, 1, 4, 24, 48 and 72 h. The biodistribution study indicated a maximal brain tumor uptake at 1.75±0.12%ID/g at 24 h postinjection. Both of autoradiography and H&E staining showed a clear and correspondent tumor region. The microSPECT/CT imaging also revealed a most clearly tumor image at 24 h postinjection. From ROI analysis, the tumor-to-normal brain uptake could reach at 29-fold at 24 h postinjection. This work demonstrated that 188ReBMEDA-liposome could display a high tumor-to-normal brain ratio uptake, indicating its potential as a diagnostic and therapeutic agent for GBM. doi:10.1016/j.nucmedbio.2010.04.180 [188Re(N)(cys∼)(PNP)]+/0 mixed ligand compounds as models for target specific agents Cristina Bolzati a, Stefan Thieme b, Stefania Agostini c, Davide Carta c, Nicola Salvarese c, Fiorenzo Refosco a, R. Bergmann b, Jens Pietzsch b, Hans J. Pietzsch b a ICIS-CNR, Padua, Italy b Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, Dresden, Germany c Department Pharm. Sci. Padua University, Italy
Abstracts / Nuclear Medicine and Biology 37 (2010) 677–726 99m
[1] Maria L, Cunha S, Videira M, Gano L, Paulo A, Santos IC, et al. Dalton Trans 2007:3010-9. [2] Maria L, Fernandes C, Garcia R, Gano L, Paulo A, Santos IC, et al. Dalton Trans 2009:603-6.
olabeled peptides were evaluated in SCID female mice bearing human MDA-MB-435 breast tumors. Results: 99mTc(CO)3-DAP-GSG-KCCYSL and 99mTc(CO)3-(NαHis)AcGSG-KCCYSL were stable and bound to ErbB-2-expressing MDA-MB-435 cells. In vivo biodistribution studies revealed that tumor uptake of 99m Tc(CO)3-DAP-GSG-KCCYSL was 1.67±0.16, 1.25±0.61, 0.88±0.12, 0.30±0.06 %ID/g at 1, 2, 4, and 24 post injection, respectively. Tumor uptake of 99m Tc(CO) 3 -(NαHis)Ac-GSG-KCCYSL was 0.76±0.13, 0.75±0.40, 0.33±0.08, 0.16±0.02 %ID/g at 1, 2, 4, and 24 post injection, respectively. SPECT/computed tomographic studies showed tumor selective uptake of both the peptides in the tumor-bearing mice. Specific uptake was confirmed by competitive receptor blocking studies. Conclusions: 99mTc(CO)3-DAP-GSG-KCCYSL and 99mTc(CO)3-(NαHis) Ac-GSG-KCCYSL have the potential to be used as tumor imaging probes. Research Support: National Institutes of Health 1R-21CA137239-01A1 and a Merit Review Award from the Veterans Administration.
doi:10.1016/j.nucmedbio.2010.04.103
doi:10.1016/j.nucmedbio.2010.04.136
ethanamine and tris(pyrazolyl)methane Tc-tricarbonyl complexes (1a– 5a) were synthesized and its potential interest for tumor detection evaluated in human cancer cell lines of different etiology. Herein, we will present the in vitro uptake and efflux kinetic studies undertaken and the results will be compared with those obtained for 99mTc-Sestamibi and 99mTc-Tetrofosmin. For the complexes presenting internalization rates and retention in tumor cells higher than found for 99mTc-Sestamibi, the uptake mechanism in tumor cells was also studied and will be presented and discussed in this communication. References
Correlation between GC-C expression and uptake of GC-C-targeted imaging agents in vitro and in vivo
Trifunctional tricarbonyl complexes for cell-specific and nuclear targeting
Dijie Liu a,d, Leonard R. Forte c, Michael F. Giblin a,b,d,⁎ a Harry S. Truman Memorial Veterans Administration Hospital b Department of Radiology, University of Missouri-Columbia c Department of Medical Pharmacology and Physiology, University of Missouri-Columbia d Radiopharmaceutical Sciences Institute, University of Missouri-Columbia
Teresa Esteves a, Fernanda Marques a, José Rino b, António Paulo a, Charles J. Smith c, Isabel Santos a a UCQR, ITN, Sacavém, Portugal b IMM, FMUL, Lisboa, Portugal c Department Radiology and HSTMVH, Missouri, USA
The guanylyl cyclase C (GC-C) receptor is currently under investigation as a specific biomarker for metastatic colorectal cancer. Agonist activation of GC-C results in initiation of a signaling cascade that ultimately results in inhibition of proliferation of GC-C-expressing cells. The pharmacological use of GC-C agonists is therefore receiving increasing attention as a new paradigm for the treatment of colorectal cancer. In this study, we have correlated GC-C expression in three colorectal cancer cell lines with uptake of molecular imaging agents targeting GC-C in vitro and in vivo. Receptor expression in these three cell lines differs across a wide range (T84NLS174T≫HT-29), as determined by western blot and receptor binding assay. In vivo, tumor uptake of 111In-labeled GC-C agonists was found to vary according to receptor expression at both 1 and 4 hr pi. Molecular imaging with GC-C-specific radiopharmaceuticals could provide a practical method of selection of subpopulations of individuals who may benefit from treatment with GC-C-targeted therapeutic agents. doi:10.1016/j.nucmedbio.2010.04.149 Evaluation of [99mTc(CO)3]-labeled ErbB-2-targeting peptides for breast carcinoma imaging Susan L. Deutscher Department of Biochemistry, University of Missouri and Research Service, Harry S. Truman Veterans Memorial Hospital, Columbia, MO, USA Objectives: The purpose of this study was to radiolabel a novel ErbB-2-avid peptide, discovered from bacteriophage display, with [99mTc(H2O)3(CO)3]+ and evaluate the in vitro cellular targeting and in vivo tumor imaging properties of the peptide in a mouse model of human breast cancer. Methods: The peptide, KCCYSL, synthesized with the chelates diaminopropionc acid (DAP) or Nα-histidinyl acetic acid [(NαHis)Ac] at its aminoterminus, was radiolabeled with [99mTc(H2O)3(CO)3]+. The radiochemical stabilities of the peptides were assessed and in vitro binding to MDA-MB435 human breast carcinoma cells was analyzed. Biodistributions and single photon emission computed tomographic (SPECT) imaging of the radi-
Novel structures labeled with Auger emitters, such as 99mTc, with high affinity for receptors expressed on tumor cells and directed at the nucleus of those cells may have therapeutic potential. Additionally, the introduction of a DNA-binding and/or fluorescent groups in the same molecule may improve the therapeutic effect and will allow to follow the trafficking and fate of the compounds at the cellular and subcellular level. Alberto et al., pioneered the design of Re and Tc complexes bearing a DNA-binding group that can reach the nucleus of given cells without the need of a nuclear localization signal [1]. Using murine melanoma cells, we have also shown that nuclear targeting and radiotoxicity effects can be achieved with tricarbonyl complexes anchored by pyrazolyl-diamine ligands bearing DNA-binding groups [2,3]. In order to make such compounds cell-specific, trifunctional tricarbonyl complexes bearing fluorescent DNA-intercalators and bombesin analogues have been isolated, characterized and biologically evaluated. Herein, we will report on these novel trifunctional tricarbonyl complexes which are cell-specific and target the nucleus. References [1] Alberto, et al. Chem Eur J 2007;13:3842. [2] Santos, et al. Chem Bio Chem 2008;9:131-42. [3] Santos, et al. Cancer Biother Radiopharm 2009;5:1-13. doi:10.1016/j.nucmedbio.2010.04.065 The preparation of 99mTc-DTPA-LSA and its instant lyophilized kit for hepatic receptor imaging Wenjiang Yang, Xianzhong Zhang⁎, Xuebin Wang, Zhigang Tang Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China Introduction: 99mTc-DTPA-LSA was developed for hepatic receptor imaging. Methods: Neolactosylated human serum albumin (LSA) was prepared by covalent coupling lactose to HSA using reductive amination method. Bifunctional chelator diethylenetriamine pentaacetic acid (DTPA) was
Abstracts / Nuclear Medicine and Biology 37 (2010) 677–726 introduced to LSA via DTPA anhydride. DTPA-LSA was labeled with technetium-99m by using SnCl2 as reductant and labeling conditions of 99mTcDTPA-LSA were optimized. Lyophilized kit of DTPA-LSA was also developed for instant preparing of 99mTc-DTPA-LSA. Results: Technetium labeling yields in excess of 93% by using both of liquid and lyophilized labeling methods. Biodistribution of 99mTc-DTPA-LSA was investigated in both normal and liver-injury model mice. It showed high liver uptake in normal mice (N96%ID·g−1 at 5 min after injection), and it could be blocked significantly by pre-injecting free NGA. The liver uptake of 99mTcDTPA-LSA in liver-injury model mice was lower than that of normal mice (P=.0149). Conclusions: The promising biological properties of 99mTc-DTPA-LSA combined with the development of reliable and instant lyophilized DTPALSA kit afford the opportunity of hepatic receptor imaging for routine clinical assessment of hepatocyte function. The project was sponsored by SRF for ROCS and SEM and supported partially by the Scientific Research Foundation of Beijing Normal University. doi:10.1016/j.nucmedbio.2010.04.008
711
99m
and Tc-HEDP, for bone imaging [1]. Since aminobisphosphonates are very polar drugs with low membrane permeability, new amino acid derivatives have been synthesized in order to improve bioavailability and potency [2,3]. Aiming at the preparation of novel radioactivity delivery systems for target therapy (e.g., 188/186 Re) or diagnostic (99mTc) of bone diseases, herein we describe the synthesis and characterization of new glutamic acid derivatives containing a bisphosphonate unit.
References [1] Fleish H. Bisphosphonates in bone disease. In: Fleish H, editor. From the Laboratory to the Patient. 2nd ed. New York (NY): The Parthenon Publishing Group; 1995. [2] Ezra A, Golomb G. Administration routes and delivery systems of bisphosphonates for the treatment of bone resorption. Adv Drug Del Rev 2000;42:175. [3] Mizrahi DM, Wagner T, Segall Y. α-amino acid derived bisphosphonates. Synthesis and anti-resorptive activity. Phosphorus Sulfur Silicon 2001;173:1.
Synthesis and evaluation of a novel folate derivative labeled with 99mTc
doi:10.1016/j.nucmedbio.2010.04.137
Yan Pang, Hongjuan Guo, Meilin Zhu, Fang Xie, Jie Lu Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education; College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China
Development of 188Re-BMEDA encapsulated PEGylated liposome as a diagnostic and therapeutic agent for glioma
The folate receptor (FR) is over expressed in many human tumor, but present in low in most normal tissues and organs. Therefore, folate derivatives labeled with radionuclides could be used for tumor diagnosis and therapy. In this report, a novel folate-HYNIC conjugate (FA-NHHN-HYNIC) was synthesized and labeled with 99mTc using tricine and 99mTc(HYNIC-NHHN-FA)(Tricine) (TPPTS) as coligands. TPPTS was purified by high-performance liquid chromatography for in vitro/in vivo experiments. This hydrophilic complex was stable both in saline and serum. Cell binding experiments revealed that the complex can be taken and internalized by FR-positive KB tumor cells; meanwhile, the accumulation was blocked with excess folic acid. In vivo biodistribution in athymic nude mice bearing KB tumor cells showed that the complex had high uptakes in FR-positive tumor (9.79±1.66% ID/g, 4 h after injection) and blockade studies confirmed specific accumulation of the radiotracer. The accumulation in other non-targeted tissues and organs were low, tumor-to-blood and tumor-to-muscle ratios reached 35.80±10.05 and 10.55±3.71 at 4 h after injecting, respectively. This complex could be a potent agent for folate receptor imaging. Acknowledgments This work was supported by the National Natural Science Foundation of China (20701004). doi:10.1016/j.nucmedbio.2010.04.003 1-Hydroxybisphosphonate-containing amino acids for radioactivity delivery Elisa Palma, João D.G. Correia, Lurdes Gano, Isabel Santos U.C.Q.R., Instituto Tecnológico e Nuclear, Estrada Nacional 10, 2686-953 Sacavém, Portugal Geminal bisphosphonates are a class of compounds that present very high affinity for the bone mineral matrix because they bind strongly to its main component, the hydroxyapatite crystals. Some bisphosphonates have been approved for clinical use in Paget's disease, hypercalcemia of malignancy and osteoporosis. They are also used in the preparation of 99mTc-radiopharmaceuticals, such as 99mTc-MDP
Feng-Yun Huang a, Te-Wei Leeb, Chih-Hao K. Kaoc, Chih-Hsien Chang b, Wan-Yu Lee a, Way-Yi Chen a, Jem-Mau Lo a a Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan b Institute of Nuclear Energy Research, Longtan, Taiwan c Department of Radiopharmaceutical Production, Tzu Chi General Hospital, Hualien, Taiwan 188
Re-N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA) was encapsulated into the PEGylated liposome to produce the 188ReBMEDA-liposome nanoparticles sized at 85±20 nm in diameter. Radiochemical yield of 188Re-BMEDA-liposome could achieve ≥85%. The agent was administrated into the orthotopic F344/F98 brain glioma tumor bearing animal model via tail vein. Biodistribution study, mirco-single photon emission computed tomography/computed tomographic (SPECT/ CT) imaging, autoradiography and hematoxylin and eosin (H&E) staining were carried out at varying postinjection time points, 1, 4, 24, 48 and 72 h. The biodistribution study indicated a maximal brain tumor uptake at 1.75±0.12%ID/g at 24 h postinjection. Both of autoradiography and H&E staining showed a clear and correspondent tumor region. The microSPECT/CT imaging also revealed a most clearly tumor image at 24 h postinjection. From ROI analysis, the tumor-to-normal brain uptake could reach at 29-fold at 24 h postinjection. This work demonstrated that 188ReBMEDA-liposome could display a high tumor-to-normal brain ratio uptake, indicating its potential as a diagnostic and therapeutic agent for GBM. doi:10.1016/j.nucmedbio.2010.04.180 [188Re(N)(cys∼)(PNP)]+/0 mixed ligand compounds as models for target specific agents Cristina Bolzati a, Stefan Thieme b, Stefania Agostini c, Davide Carta c, Nicola Salvarese c, Fiorenzo Refosco a, R. Bergmann b, Jens Pietzsch b, Hans J. Pietzsch b a ICIS-CNR, Padua, Italy b Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, Dresden, Germany c Department Pharm. Sci. Padua University, Italy