Preclinical evaluation of [(124)I]-sotorasib for the imaging of Kirsten rat sarcoma G12C mutant tumors Journal Article
| Authors: | Artschwager, R.; Kalidindi, T. M.; Johnson, D.; Brennan, C.; Samuels, Z. V.; Lito, P.; Pillarsetty, N. V. K. |
| Article Title: | Preclinical evaluation of [(124)I]-sotorasib for the imaging of Kirsten rat sarcoma G12C mutant tumors |
| Abstract: | Kirsten rat sarcoma (KRAS) is a frequently mutated oncogene responsible for several oncogenic KRAS variants and for driving tumor proliferation. Some nonsmall cell lung cancer (NSCLC) tumors exhibit KRAS G12C mutations, which can be targeted for inhibition using covalent and more recently noncovalent inhibitors. Sotorasib was the first FDA-approved G12C inhibitor that has shown efficacy in lung cancer patients, but with mixed responses. The lack of efficacy can be attributed to tumor heterogeneity (lack of G12C mutations) and/or inefficient delivery. Targeted KRAS G12C imaging has potential to identify NSCLC lesions with the targeted mutation and elucidate the oncogene’s role in driving tumor growth and correlating responses to treatment. Toward this goal, we have developed a sotorasib-based molecular agent for PET imaging and tested its efficacy in targeting tumor lesions with KRAS G12C mutations. Here, we describe the synthesis, in vitro and in vivo evaluation of an [124I]I-Sotorasib analog in targeting G12C mutant tumor lesions using PET imaging. © 2024 American Chemical Society. |
| Keywords: | controlled study; gene mutation; cancer growth; nonhuman; positron emission tomography; mouse; animal tissue; animal experiment; animal model; in vivo study; in vitro study; sarcoma; rat; imaging; iodine 124; k ras protein; pet; non small cell lung cancer; female; article; kras g12c; sotorasib |
| Journal Title: | ACS Pharmacology & Translational Science |
| Volume: | 7 |
| Issue: | 12 |
| ISSN: | 2575-9108 |
| Publisher: | American Chemical Society |
| Date Published: | 2024-12-13 |
| Start Page: | 3867 |
| End Page: | 3878 |
| Language: | English |
| DOI: | 10.1021/acsptsci.4c00425 |
| PROVIDER: | scopus |
| PMCID: | PMC11650727 |
| PUBMED: | 39698284 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK authors: Raik Artschwager and Naga Vara Kishore Pillarsetty -- There is a typo in the grant, it's displayed as P30 CA08748 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work