2020 Fiscal Year Annual Research Report
New strategy of diagnostic imaging probes prior to administrating molecular target drugs
| Project/Area Number |
20K16722
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| Research Institution | Kanazawa University |
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Principal Investigator |
Effendi Nurmaya 金沢大学, 新学術創成研究機構, 特任助教 (60842911)
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| Project Period (FY) |
2020-04-01 – 2021-03-31
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| Keywords | imaging / PDGFRb / EGFR / Osimertinib / Peptide |
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| Outline of Annual Research Achievements |
Tyrosine kinase receptors (TKRs) are transmembrane proteins consisting of the extracellular domain for ligand binding and the intracellular part for signaling. This study aims to develop radiolabeled probes targeting TKRs for imaging and therapy.
1. Seven radiotracers, 67Ga-DOTA-linker-IPLPPPRRPFFK peptides with different lengths and types of linkers, were designed, synthesized, and evaluated as platelet-derived growth factor receptor beta (PDGFRb) imaging agents. Two radiotracers were chosen based on the result of in vitro studies and continued in vivo studies. [67Ga]Ga-DOTA-EG2-IPLPPPRRPFFK and [67Ga]Ga-DOTA-EG4-IPLPPPRRPFFK showed the tumor-to-blood ratios were 2.61±0.75 and 2.05±0.77, respectively at 1h post-injection. Co-injection of [67Ga]Ga-DOTA-EG2-IPLPPPRRPFFK and an excess amount of IPLPPPRRPFFK peptide as a blocking agent can significantly decrease this ratio. However, tumor accumulation was not considered sufficient. Therefore, further probe modification is required to assess tumor accumulation for in vivo imaging.
2. The aim of this study is developing radiohalogenated-Osimertinib conjugated with a recombinant human IgG1 mAb Necitumumab and/or its fragment Necitumumab-derived Fab, which possess high binding affinity and specificity toward EGFR. In the first year, Osimertinib, Br-Osimertinib, I-Osimertinib, and three enzyme-cleavable linkers (Mc-Val-Cit-PABOH, Mc-Val-Ala-PABOH, and Mc-Phe-Ala-PABOH) were prepared.
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