2022 Fiscal Year Final Research Report
New strategy of diagnostic imaging probes prior to administrating molecular target drugs
Project/Area Number |
20K16722
|
Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 52040:Radiological sciences-related
|
Research Institution | Kanazawa University |
Principal Investigator |
Effendi Nurmaya 金沢大学, 新学術創成研究機構, 研究協力員 (60842911)
|
Project Period (FY) |
2021-11-01 – 2023-03-31
|
Keywords | Imaging / Osimertinib / Peptide / EGFR / PDGFRb / TKI / NSCLC |
Outline of Final Research Achievements |
Tyrosine kinase receptors (TKRs) are transmembrane proteins consisting of the extracellular domain for ligand binding and the intracellular part for signaling. PDGFRβ and 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 result 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 tumor was higher than in blood and muscle. Due to high lung uptake than tumor, the probe's structure needs to be modified. To visualize EFGR with mutation, a novel probe peptide-osimertinib-conjugated compound containing an enzyme-cleavable linker is currently being synthesized and evaluated.
|
Free Research Field |
Radiological sciences-related
|
Academic Significance and Societal Importance of the Research Achievements |
Overexpression of PDGFRβ and EGFR as the subfamilies of TKRs associated with various human cancer. Imaging agents targeting PDGFRβ and mutated-EGFR can help determine their expression level via imaging to optimize and evaluate the effectiveness of treatment outcomes.
|