- Email: [email protected]
A comparative study of 64Cu-NO2A-Bombesin antagonist and agonist ligands
Abstracts / Nuclear Medicine and Biology 37 (2010) 677–726 SSTR2 transduced animals showed a three- to fourfold increase in muscle uptake compared to controls. The increase in 68Ga-DOTATATE uptake was AAV dose dependent. Liver transduced animals showed a tendency for reduction in liver uptake over time whereas muscle transduced animals showed stable uptake levels for 6 months. Loss of expression in liver may be mediated by an autoimmune response, therefore AAV-TBG-SSTR2 was also injected into athymic nude mice. In these animals, 68Ga-DOTATATE uptake in liver is markedly higher than in controls, and there is no evidence in reduction of uptake in the three month observation period. Evaluation of gene transfer is feasible with the described approach and may be useful for quantitative monitoring of gene therapy in animal models.
725
Pimonidazole uptake and HIF-1α expression matched radiosensitivity better than the PET tracers. Significant uptake of the PET tracers occurred only at extreme hypoxia, well below the pO2 at which radiation resistance became significant. The results imply that a significant fraction of radioresistant cells will not take up tracer because they are not hypoxic enough. Thus the tracers are likely to underestimate radioresistance due to hypoxia. New tracers are needed whose uptake/pO2 profile better matches the radioresistance profile in order to more accurately estimate the radioresistance due to hypoxia. doi:10.1016/j.nucmedbio.2010.04.109
doi:10.1016/j.nucmedbio.2010.04.040 Cu-galectin-3-specific peptide as an in vivo PET imaging agenti
64
Imaging changes of p-glycoprotein activity in vivo with 68 Ga-Schiff base Marco Fellnera, Wolfgang Dillenburgb, Frank Röscha, Oliver Thewsb a COSTD38-WG3, Institute of Nuclear Chemistry, Mainz, Germany b Institute of Physiology and Pathophysiology, COSTD38-WG3, Mainz, Germany P-glycoprotein (pGP) pumps a wide number of xenobiotics out of the cell leading to multidrug resistance in many tumours. It was shown in vitro that pGP activity can be increased by extracellular acidosis. Here mitogen-activated protein kinases (MAPKs) (p38, ERK1/2) seem to play an important role. With the Schiff base complex 68Ga-MFL6.MZ it became possible to visualize the activity of pGP in vivo by μ-positron emission tomography (PET). MFL6.MZ was labelled with 68Ga. Animal studies were performed with tumour-bearing Copenhagen rats. Acidification was achieved by direct tumour injection of small amounts of lactic acid, respectively SB203580 (p38) and U0126 (ERK1/2) for MAPK inhibition. Acidifying the tumour reduces the tracer accumulation indicating a higher pGP activity (80% compared to control tumours). MAPK inhibitors reduced the pGP transport rate which resulted in a higher tracer accumulation. SB203580 (p38) led to doubling the tracer activity, whereas with U0126 (ERK1/2) the concentration increased by 30%. The PET tracer 68Ga-MFL6.MZ indicates that pGP is markedly activated under acidic environment. The p38-MAPK pathway plays an important role for pGP regulation in vivo, whereas ERK1/2 is of minor importance. From these results new strategies for overcoming multidrug resistance (e.g., inhibition of p38) may be developed.
Susan L. Deutscher a,b, Senthil R. Kumar b, Thomas P. Quinn b a Research Division, Harry S. Truman Veterans Hospital, Columbia, MO 65201, USA b Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA Objectives: The purpose of our study was to evaluate a phage display identified galectin-3 (gal-3) avid peptide G3-C12 (ANTPCGPYTHDCPCKR) as a positron emission tomography (PET) imaging agent for gal-3 expressing breast tumors. Methods: The chelator CB-TE2A was attached to the N-terminus of G3-C12 for labeling with 64Cu. Cell binding studies with human gal-3 positive MDA-MB435 breast carcinoma cells and normal mammary cells were performed. In vivo biodistribution and PET imaging were analyzed in SCID mice bearing MDAMB-435 tumor xenografts. Results: 64Cu-CB-TE2A- G3-C12 peptide bound to human breast carcinoma cells with an IC50 of 130±10.2 nM. In vivo biodistribution studies demonstrated radiolabeled peptide accumulation in MDA-MB-435 tumorbearing SCID mice (∼1.0% ID/g, at 2 h). Uptake of radiolabeled peptide in the liver, intestines and lungs was low at ∼0.97% ID/g, ∼0.36% ID/g and ~0.29% ID/g, respectively at 2 h, while kidney uptake was high N20% ID/g. PET imaging studies of 64Cu-labeled CB-TE2A-peptide revealed good tumor uptake after 2 h post injection. Conclusions: Our results indicate that 64Cu-CB-TE2A-G3-C12 can be developed as a PET radiotracer for gal-3 expressing tumors. doi:10.1016/j.nucmedbio.2010.04.054
doi:10.1016/j.nucmedbio.2010.04.147 Can PET hypoxia tracers predict radioresistance? Kazumi Chia⁎, Amanda J. Weeks, Rowena L. Paul, Marcel Cleij, Philip J. Blower King's College London, Division of Imaging Sciences, Rayne Institute, St. Thomas' Hospital, SE1 7EH London, UK In positron emission tomography (PET) hypoxia imaging, it is not clear whether the pO2 at which cells “switch” from low to high tracer uptake match that at which they “switch” from radiation sensitive to resistant. The aim of this work is to define the relationship between hypoxia tracer uptake (Cu-64labelled ATSM, ATS, ATSE, DTS, DTSE, DTSM, F-18-FMISO), radiosensitivity, pimonidazole, and HIF-1α at different pO2. All experiments were performed using the same hypoxia apparatus. Radiosensitivity was assessed by clonogenic assay and tracer uptake by gamma counting. Pimonidazole was measured by flow cytometry and HIF1α levels by Western blotting. Radiosensitivity started to decrease as pO2 dropped below 25 mmHg. All tracers showed hypoxia-selective uptake at levels below 2 mmHg, except for CuDTSE where it increased at 6 mmHg. By contrast, pimonidazole uptake and HIF-1α expression plateaued at 8 mmHg.
i Research support: National Institutes of Health grants P50CA103130-01 and 1R-21CA137239-01A1 and a Merit Review Award from the Veterans Administration.
A comparative study of agonist ligands
64
Cu-NO2A-Bombesin antagonist and
Charles Jeffrey Smith a,b, Prasant K. Nanda a, Stephanie Lane a, Gary L. Sieckman b, Timothy J. Hoffman a,b, Tammy Rold b a University of Missouri-Columbia School of Medicine, Columbia, MO 65211, USA b Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA Gastrin-releasing peptide receptors (GRPr) are highly expressed on many types of human cancer cells including prostate cancer. Bombesin (BBN) is a 14-amino-acid peptide that binds the GRPr with very high affinity and specificity. The aim of this study is to develop new 64Cu-labeled BBN analogs having high tumor uptake and optimal pharmacokinetics for specific targeting and molecular imaging of human prostate cancer. In this study, we describe the synthesis, characterization, and in vitro and in vivo studies of
726
Abstracts / Nuclear Medicine and Biology 37 (2010) 677–726 Platinum chemotherapeutics are used extensively as a first line treatment in [ Cu-NO2A-X-[DPhe ]-BBN(6-13)NHEt and 64Cu-NO2A-X-BBN(7-14) over 28% of all cancers and widely as a second line treatment in combination NH2 where NO2A=,4,7-triazacyclononane-1,4,-diacetic acid and X=Parawith biological markers such as Herceptin. Over 20% of patients will aminobenzoic acid, 6-aminohexanoic acid, 8-aminooctanoic acid and 9experience maximum tolerate dose and significant side effects because nonanoic acid. All of the new conjugates were radiolabeled and purified dosage is often estimated using unreliable and indirect methods such as by reverse-phase high-performance liquid chromatography. Complete and surface area and glomerular filtration rates. We are interested in providing a full characterization of natCu-BBN conjugates was done using electromolecular imaging tool that allows the physician to screen a patient, monitor spray-ionization mass spectrometry. Competitive displacement binding response and drug resistance and to personalise treatment regimes in order to assays indicated that all of the conjugates exhibited IC50s in the nM range reduce side effects. in human, prostate PC-3 cells. Biodistribution studies using these new The ability to produce platinum radiopharmaceuticals commercially has conjugates in rodents bearing PC-3 xenografted tumors indicated rapid been limited by long and unreliable synthetic processes. We have developed clearance of targeting vector from blood with high uptake and retention in patent technology for the production of reactor base platinum radiotumors. Molecular imaging studies in rodents produced high-contrast, pharmaceuticals, such as 195mPt-cisplatin and 195mPt-carboplatin. This study high-quality micro-positron emission tomography images with very high reports the neutron activation of 194platinum target material in the new tumor-to-background ratios. research reactor OPAL and validation of the production of multiple (five) doi:10.1016/j.nucmedbio.2010.02.012 patient batches for both 195mcisplatin and 195mcarbplatin. Yields were 53±3% and 29±4%, respectively, with specific activities of up to 8 MBq/mg. Comparison of 68Ga-siderophores for imaging Aspergillus fumigatus Production times were dramatically reduced from up to 24 h to less than 3 h infections with PET using the new process. 64
6
Milos Petrik, Hubertus Haas, Anna Helbok, Michael Blatzer, Markus Schrettl, Cornelia Lass-Floerl, Clemens Decristoforo COSTBM0607-WG2, Medical University Innsbruck, Austria 68
We have recently shown that Ga-labelled siderophores can serve as specific positron emission tomography imaging agents for Aspergillus fumigatus infections (JNM 2010, 51:639-45). We report here on the direct comparison of different 68Ga-labelled siderophores for A. fumigatus infection imaging. 68 Ga-labelling of different siderophores (TAFC, FC, FCH, COP, FOXE, FOXB) was performed using acetate buffer with varying amounts of siderophores. Stability and RCP was tested by RP-HPLC in serum, towards DTPA and iron, protein binding and log P values were determined. In vitro uptake and release were tested using iron deficient and replete A. fumigatus cultures. Biodistribution was studied in mice and in a rat A. fumigatus infection model. Differences among siderophores were observed in labelling efficiency and stability. All 68Ga-siderophores revealed hydrophilic properties with low protein binding for 68Ga-TAFC, 68Ga-COP, 68Ga-FOXE and 68GaFOXB (b10%) and high for 68Ga-FC and 68Ga-FCH (~60%). Uptake in A. fumigatus cultures was dependent on the mycelial iron load and type of siderophore, low values were found for 68Ga-FOXB and 68Ga-COP. Rapid renal excretion and low retention were found for derivatives with low protein binding, significant uptake of 68Ga-TAFC was found in A. fumigatus infected lungs. This work revealed that a number of different siderophores bind 68Ga with high affinity and stability. Especially 68Ga-TAFC and 68Ga-FOXE are promising candidates for A. fumigatus infections imaging with low values of protein binding and high and specific uptake in A. fumigatus cultures. Further studies are currently ongoing. doi:10.1016/j.nucmedbio.2010.04.116 Multiple patient batch production of 195mPt cisplatin and 195mPt carboplatin for use in drug risk assessment and optimisation of patient dose Gary Perkins, Suzanne V. Smith Australian Nuclear Science and Technology Organisation, Kirrawee, DC, Australia
doi:10.1016/j.nucmedbio.2010.04.145 45
Ti-cations as potential PET tracers for cerebral neurodegeneration
D. Salber a, J. Manuvelpillai a, I. Spahn b, S. Klein a, F. Uhlenbrock, C. Palm c,f, A. Matusch d, S. Becker e, K.-J. Langen a, H.H. Coenen b, a Institute of Neurosciences and Medicine, INM-4 b Institute of Neurosciences and Medicine, INM-5 c Institute of Neurosciences and Medicine, INM-1 d Institute of Neurosciences and Medicine, INM-2 e Central Division of Analytical Chemistry, ZCH, Forschungszentrum Jülich, Wilhelm-Johnen-Str., 52425 Jülich, Germany f University of Applied Sciences Regensburg, Faculty of Computer Sciences and Mathematics, Universitätsstr., 93053 Regensburg, Germany Cortical infarctions may lead to secondary degeneration of thalamo-cortical projection neurons. Using magnetic resonance imaging, a chronic accumulation of iron was observed in those thalamic areas (Justicia, 2008). Therefore, we analyzed the regional content of (various) metals in rat brain slices at different time points (1, 5, 7, 17, 21, 28, 42 days) after cortical infarctions by LA-ICP-MS (www.brainmet.com). Surprisingly, the correlation of natural titanium and neurodegeneration was most striking. Up to 3 weeks, a constant accumulation in the cortical infarct shows a lesion/brain quotient of 43.78±0.97 (cisFDPro: 11.4±4.4), while in the area of secondary degenerating neurons, a maximum accumulation is achieved with a quotient of 8.43±0.88 at Day 17 (cisFDPro:7,2±1.9). Areas of neurodegeneration were localized by immunofluorescence staining of reactive microgliosis and by autoradiography with the positron emission tomography (PET) tracer Dcis-18FPro (Langen, 2005). In order to investigate the accumulation of titanium in those neurodegenerative tissues in vivo by PET, the positron-emitter titanium-45 (T1/2=3.08 h) was produced by the 45Sc(p,n)45Ti nuclear reaction and applied to the rat model. The radiochemical separation and the synthesis of 45Ti citrate were done according to Vavere et al. (2005) who earlier demonstrated in vivo binding of 45Ti-ions to transferrin and accumulation in peripheral tumors. First experiments so far showed distinct uptake in lesioned areas within 2 h. doi:10.1016/j.nucmedbio.2010.04.171
725
Pimonidazole uptake and HIF-1α expression matched radiosensitivity better than the PET tracers. Significant uptake of the PET tracers occurred only at extreme hypoxia, well below the pO2 at which radiation resistance became significant. The results imply that a significant fraction of radioresistant cells will not take up tracer because they are not hypoxic enough. Thus the tracers are likely to underestimate radioresistance due to hypoxia. New tracers are needed whose uptake/pO2 profile better matches the radioresistance profile in order to more accurately estimate the radioresistance due to hypoxia. doi:10.1016/j.nucmedbio.2010.04.109
doi:10.1016/j.nucmedbio.2010.04.040 Cu-galectin-3-specific peptide as an in vivo PET imaging agenti
64
Imaging changes of p-glycoprotein activity in vivo with 68 Ga-Schiff base Marco Fellnera, Wolfgang Dillenburgb, Frank Röscha, Oliver Thewsb a COSTD38-WG3, Institute of Nuclear Chemistry, Mainz, Germany b Institute of Physiology and Pathophysiology, COSTD38-WG3, Mainz, Germany P-glycoprotein (pGP) pumps a wide number of xenobiotics out of the cell leading to multidrug resistance in many tumours. It was shown in vitro that pGP activity can be increased by extracellular acidosis. Here mitogen-activated protein kinases (MAPKs) (p38, ERK1/2) seem to play an important role. With the Schiff base complex 68Ga-MFL6.MZ it became possible to visualize the activity of pGP in vivo by μ-positron emission tomography (PET). MFL6.MZ was labelled with 68Ga. Animal studies were performed with tumour-bearing Copenhagen rats. Acidification was achieved by direct tumour injection of small amounts of lactic acid, respectively SB203580 (p38) and U0126 (ERK1/2) for MAPK inhibition. Acidifying the tumour reduces the tracer accumulation indicating a higher pGP activity (80% compared to control tumours). MAPK inhibitors reduced the pGP transport rate which resulted in a higher tracer accumulation. SB203580 (p38) led to doubling the tracer activity, whereas with U0126 (ERK1/2) the concentration increased by 30%. The PET tracer 68Ga-MFL6.MZ indicates that pGP is markedly activated under acidic environment. The p38-MAPK pathway plays an important role for pGP regulation in vivo, whereas ERK1/2 is of minor importance. From these results new strategies for overcoming multidrug resistance (e.g., inhibition of p38) may be developed.
Susan L. Deutscher a,b, Senthil R. Kumar b, Thomas P. Quinn b a Research Division, Harry S. Truman Veterans Hospital, Columbia, MO 65201, USA b Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA Objectives: The purpose of our study was to evaluate a phage display identified galectin-3 (gal-3) avid peptide G3-C12 (ANTPCGPYTHDCPCKR) as a positron emission tomography (PET) imaging agent for gal-3 expressing breast tumors. Methods: The chelator CB-TE2A was attached to the N-terminus of G3-C12 for labeling with 64Cu. Cell binding studies with human gal-3 positive MDA-MB435 breast carcinoma cells and normal mammary cells were performed. In vivo biodistribution and PET imaging were analyzed in SCID mice bearing MDAMB-435 tumor xenografts. Results: 64Cu-CB-TE2A- G3-C12 peptide bound to human breast carcinoma cells with an IC50 of 130±10.2 nM. In vivo biodistribution studies demonstrated radiolabeled peptide accumulation in MDA-MB-435 tumorbearing SCID mice (∼1.0% ID/g, at 2 h). Uptake of radiolabeled peptide in the liver, intestines and lungs was low at ∼0.97% ID/g, ∼0.36% ID/g and ~0.29% ID/g, respectively at 2 h, while kidney uptake was high N20% ID/g. PET imaging studies of 64Cu-labeled CB-TE2A-peptide revealed good tumor uptake after 2 h post injection. Conclusions: Our results indicate that 64Cu-CB-TE2A-G3-C12 can be developed as a PET radiotracer for gal-3 expressing tumors. doi:10.1016/j.nucmedbio.2010.04.054
doi:10.1016/j.nucmedbio.2010.04.147 Can PET hypoxia tracers predict radioresistance? Kazumi Chia⁎, Amanda J. Weeks, Rowena L. Paul, Marcel Cleij, Philip J. Blower King's College London, Division of Imaging Sciences, Rayne Institute, St. Thomas' Hospital, SE1 7EH London, UK In positron emission tomography (PET) hypoxia imaging, it is not clear whether the pO2 at which cells “switch” from low to high tracer uptake match that at which they “switch” from radiation sensitive to resistant. The aim of this work is to define the relationship between hypoxia tracer uptake (Cu-64labelled ATSM, ATS, ATSE, DTS, DTSE, DTSM, F-18-FMISO), radiosensitivity, pimonidazole, and HIF-1α at different pO2. All experiments were performed using the same hypoxia apparatus. Radiosensitivity was assessed by clonogenic assay and tracer uptake by gamma counting. Pimonidazole was measured by flow cytometry and HIF1α levels by Western blotting. Radiosensitivity started to decrease as pO2 dropped below 25 mmHg. All tracers showed hypoxia-selective uptake at levels below 2 mmHg, except for CuDTSE where it increased at 6 mmHg. By contrast, pimonidazole uptake and HIF-1α expression plateaued at 8 mmHg.
i Research support: National Institutes of Health grants P50CA103130-01 and 1R-21CA137239-01A1 and a Merit Review Award from the Veterans Administration.
A comparative study of agonist ligands
64
Cu-NO2A-Bombesin antagonist and
Charles Jeffrey Smith a,b, Prasant K. Nanda a, Stephanie Lane a, Gary L. Sieckman b, Timothy J. Hoffman a,b, Tammy Rold b a University of Missouri-Columbia School of Medicine, Columbia, MO 65211, USA b Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA Gastrin-releasing peptide receptors (GRPr) are highly expressed on many types of human cancer cells including prostate cancer. Bombesin (BBN) is a 14-amino-acid peptide that binds the GRPr with very high affinity and specificity. The aim of this study is to develop new 64Cu-labeled BBN analogs having high tumor uptake and optimal pharmacokinetics for specific targeting and molecular imaging of human prostate cancer. In this study, we describe the synthesis, characterization, and in vitro and in vivo studies of
726
Abstracts / Nuclear Medicine and Biology 37 (2010) 677–726 Platinum chemotherapeutics are used extensively as a first line treatment in [ Cu-NO2A-X-[DPhe ]-BBN(6-13)NHEt and 64Cu-NO2A-X-BBN(7-14) over 28% of all cancers and widely as a second line treatment in combination NH2 where NO2A=,4,7-triazacyclononane-1,4,-diacetic acid and X=Parawith biological markers such as Herceptin. Over 20% of patients will aminobenzoic acid, 6-aminohexanoic acid, 8-aminooctanoic acid and 9experience maximum tolerate dose and significant side effects because nonanoic acid. All of the new conjugates were radiolabeled and purified dosage is often estimated using unreliable and indirect methods such as by reverse-phase high-performance liquid chromatography. Complete and surface area and glomerular filtration rates. We are interested in providing a full characterization of natCu-BBN conjugates was done using electromolecular imaging tool that allows the physician to screen a patient, monitor spray-ionization mass spectrometry. Competitive displacement binding response and drug resistance and to personalise treatment regimes in order to assays indicated that all of the conjugates exhibited IC50s in the nM range reduce side effects. in human, prostate PC-3 cells. Biodistribution studies using these new The ability to produce platinum radiopharmaceuticals commercially has conjugates in rodents bearing PC-3 xenografted tumors indicated rapid been limited by long and unreliable synthetic processes. We have developed clearance of targeting vector from blood with high uptake and retention in patent technology for the production of reactor base platinum radiotumors. Molecular imaging studies in rodents produced high-contrast, pharmaceuticals, such as 195mPt-cisplatin and 195mPt-carboplatin. This study high-quality micro-positron emission tomography images with very high reports the neutron activation of 194platinum target material in the new tumor-to-background ratios. research reactor OPAL and validation of the production of multiple (five) doi:10.1016/j.nucmedbio.2010.02.012 patient batches for both 195mcisplatin and 195mcarbplatin. Yields were 53±3% and 29±4%, respectively, with specific activities of up to 8 MBq/mg. Comparison of 68Ga-siderophores for imaging Aspergillus fumigatus Production times were dramatically reduced from up to 24 h to less than 3 h infections with PET using the new process. 64
6
Milos Petrik, Hubertus Haas, Anna Helbok, Michael Blatzer, Markus Schrettl, Cornelia Lass-Floerl, Clemens Decristoforo COSTBM0607-WG2, Medical University Innsbruck, Austria 68
We have recently shown that Ga-labelled siderophores can serve as specific positron emission tomography imaging agents for Aspergillus fumigatus infections (JNM 2010, 51:639-45). We report here on the direct comparison of different 68Ga-labelled siderophores for A. fumigatus infection imaging. 68 Ga-labelling of different siderophores (TAFC, FC, FCH, COP, FOXE, FOXB) was performed using acetate buffer with varying amounts of siderophores. Stability and RCP was tested by RP-HPLC in serum, towards DTPA and iron, protein binding and log P values were determined. In vitro uptake and release were tested using iron deficient and replete A. fumigatus cultures. Biodistribution was studied in mice and in a rat A. fumigatus infection model. Differences among siderophores were observed in labelling efficiency and stability. All 68Ga-siderophores revealed hydrophilic properties with low protein binding for 68Ga-TAFC, 68Ga-COP, 68Ga-FOXE and 68GaFOXB (b10%) and high for 68Ga-FC and 68Ga-FCH (~60%). Uptake in A. fumigatus cultures was dependent on the mycelial iron load and type of siderophore, low values were found for 68Ga-FOXB and 68Ga-COP. Rapid renal excretion and low retention were found for derivatives with low protein binding, significant uptake of 68Ga-TAFC was found in A. fumigatus infected lungs. This work revealed that a number of different siderophores bind 68Ga with high affinity and stability. Especially 68Ga-TAFC and 68Ga-FOXE are promising candidates for A. fumigatus infections imaging with low values of protein binding and high and specific uptake in A. fumigatus cultures. Further studies are currently ongoing. doi:10.1016/j.nucmedbio.2010.04.116 Multiple patient batch production of 195mPt cisplatin and 195mPt carboplatin for use in drug risk assessment and optimisation of patient dose Gary Perkins, Suzanne V. Smith Australian Nuclear Science and Technology Organisation, Kirrawee, DC, Australia
doi:10.1016/j.nucmedbio.2010.04.145 45
Ti-cations as potential PET tracers for cerebral neurodegeneration
D. Salber a, J. Manuvelpillai a, I. Spahn b, S. Klein a, F. Uhlenbrock, C. Palm c,f, A. Matusch d, S. Becker e, K.-J. Langen a, H.H. Coenen b, a Institute of Neurosciences and Medicine, INM-4 b Institute of Neurosciences and Medicine, INM-5 c Institute of Neurosciences and Medicine, INM-1 d Institute of Neurosciences and Medicine, INM-2 e Central Division of Analytical Chemistry, ZCH, Forschungszentrum Jülich, Wilhelm-Johnen-Str., 52425 Jülich, Germany f University of Applied Sciences Regensburg, Faculty of Computer Sciences and Mathematics, Universitätsstr., 93053 Regensburg, Germany Cortical infarctions may lead to secondary degeneration of thalamo-cortical projection neurons. Using magnetic resonance imaging, a chronic accumulation of iron was observed in those thalamic areas (Justicia, 2008). Therefore, we analyzed the regional content of (various) metals in rat brain slices at different time points (1, 5, 7, 17, 21, 28, 42 days) after cortical infarctions by LA-ICP-MS (www.brainmet.com). Surprisingly, the correlation of natural titanium and neurodegeneration was most striking. Up to 3 weeks, a constant accumulation in the cortical infarct shows a lesion/brain quotient of 43.78±0.97 (cisFDPro: 11.4±4.4), while in the area of secondary degenerating neurons, a maximum accumulation is achieved with a quotient of 8.43±0.88 at Day 17 (cisFDPro:7,2±1.9). Areas of neurodegeneration were localized by immunofluorescence staining of reactive microgliosis and by autoradiography with the positron emission tomography (PET) tracer Dcis-18FPro (Langen, 2005). In order to investigate the accumulation of titanium in those neurodegenerative tissues in vivo by PET, the positron-emitter titanium-45 (T1/2=3.08 h) was produced by the 45Sc(p,n)45Ti nuclear reaction and applied to the rat model. The radiochemical separation and the synthesis of 45Ti citrate were done according to Vavere et al. (2005) who earlier demonstrated in vivo binding of 45Ti-ions to transferrin and accumulation in peripheral tumors. First experiments so far showed distinct uptake in lesioned areas within 2 h. doi:10.1016/j.nucmedbio.2010.04.171