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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 [ 124 I]I-Sotorasib analog in targeting G12C mutant tumor lesions using PET imaging., Competing Interests: The authors declare the following competing financial interest(s): NVKP is a paid consultant for Jubillant Draximage and Evergreen Theragnostics and a shareholder. All other authors have no conflict to declare., (© 2024 American Chemical Society.)