2015 Fiscal Year Annual Research Report
68Ga-Labeled Compounds for PET Myocardial Perfusion Imaging
| Project/Area Number |
15H06097
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| Research Institution | Chiba University |
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Principal Investigator |
マムード アッシュファック 千葉大学, 薬学研究科(研究院), 教授 (30754775)
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| Project Period (FY) |
2015-08-28 – 2017-03-31
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| Keywords | Molecular Imgaing / Gallium-67 / Gallium-68 / Myocardial agent |
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| Outline of Annual Research Achievements |
The objective of this study is to design, synthesize, and characterize, small-molecule chelates that form mono-cationic, lipophilic metal complexes with the Ga-67 and Ga-68 radioisotopes. These small-molecule metal complexes may have the potential to localize in myocardial tissue, and permit PET myocardial perfusion imaging.
Four separate organic hexa-dentate chelates have been synthesized and characterized. Two separate non-radioactive Ga complexes of the chelates have also been synthesized and characterized to give the desired mass specta of the mono-cationic Ga-complexes. Initial radiolabeling experiments with 67Ga have been successful in optimizing the radiolabeling conditions to achieve high radiochemical yield, obtained in 30 min of radiolabeling time. The radiolabeled complexes co-elute with the previously characterized non-radioactive complex, establishing the identity of the 67Ga complexes. Initial in-vitro stability studies, lipophilicity measurements and in-vivo biodistribution experiments are currently in progress. Analysis of the in-vivo data and comparative analysis of the structure-property and myocardial uptake studies will be conducted and guide further structural modifications of the chelate templates to optimize the Ga-complexes and obtain an effective 68Ga PET myocardial perfusion agent.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We designed, synthesized, and characterized two chelate templates based on the N2S2(bisamino-dithiol) and N2O2(diamino-bisphenol) tetradentate chelates. Using the tetra-dentate N2S2 template, we further synthesized and characterized three separate hexa-dentate chelates, with different structural elements, to introduce ethers into the molecular structure, as well as to modify the lipophilicity of the final mono-cationic complex.
Two of these bisamino-dithiol based hexadentate chelates (N4S2) have also been complexes with non-radioactive Gallium(III) and the metal complexes identified via Mass Spect. displaying the required molecular mass peak. Further characterization with NMR and X-ray crystal structure of these cold Ga-complexes is in progress. Ga-67 radiolabeling experiments to optimize radiolabeling conditions (pH, conc., temp., and time, to achieve to achieve high radiochemical yield have also been successfully achieved and display HPLC correlation of the radiolabeled 67Ga-complexes with the non-radioactive complex previously characterized.
Physiochemical properties, and in-vitro stability measurements are ongoing along with Animal bio-distribution experiments to identify the structure-activity and myocardial uptake characteristics of these Ga-complexes.
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| Strategy for Future Research Activity |
To achieve the goals of this research in the first year we successfully synthesized and characterized four(4) hexadentate chelate ligands, based on two separate N4S2 and N4O2 metal chelating scaffolds, and characterized these organic chelating systems with NMR and Mass spectroscopy. Two non-radioactive Ga-complexes were also synthesized and characterized, these non-radioactive complexes displayed the molecular mass and pattern for desired metal complexes. The full NMR and X-ray crystallographic characterization of these Gallium complexes will be completed during the next year. Additionally, along with the initial in-vivo bio-distribution and myocardial uptake studies, various physiochemical properties, such as lipophilicity, in-vitro and in-vivo stability will also be conducted with the synthesized complexes during this second year of studies. Based on the in-vivo myocardial uptake, whole body distribution and clearance data and the physiochemical properties, data obtained from the four complexes synthesized to-date, further structural modifications of the hexa-dentate ligands is envisioned to further refine the stability and physiochemical properties to optimize the metal complexes for effective myocardial uptake and imaging.
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Research Products
(1 results)
