2022 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, 研究協力員 (60842911)
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| Project Period (FY) |
2021-11-01 – 2023-03-31
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| Keywords | Imaging / Osimertinib / Peptide / EGFR / PDGFRb / TKI / NSCLC |
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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. Platelet-derived growth factor receptor β (PDGFRβ) and Epidermal growth factor receptor (EGFR) are the subfamilies of RTKs. Seven radiotracers, 67Ga-DOTA-linker-IPLPPPRRPFFK peptides, were synthesized. Their feasibility as PDGFRb imaging agents were evaluated in vitro and in vivo. [67Ga]Ga-DOTA-EG2-IPLPPPRRPFFK and [67Ga]Ga-DOTA-EG4-IPLPPPRRPFFK showed promising results than others. Two radiohalogenated Osimertinib, 125I-Osimertinib & 77Br-Osimertinib, were synthesized. Their feasibilities as imaging agents of NSCLC with L858R/T790M mutation were evaluated in vitro and in vivo. Their accumulation in tumors was higher than in blood and muscle. However, the accumulations of [125I]I-Osimertinib and [77Br]Br-Osimertinib in the lung were much higher than those in the tumors, which can interfere with the visualization of the mutation status of the NSCLC patients. Therefore, structural modification of radiohalogenated Osimertinib is still needed. To visualize EFGR with L858R/T790M mutation, a novel probe peptide-osimertinib-conjugated compound containing an enzyme-cleavable linker is currently being synthesized and evaluated.
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