New PET Tracer Noninvasively Identifies Cancer Gene Mutation for More Precise Diagnosis

Kirsten rat sarcoma (KRAS) is a mutated oncogene that is commonly found in about 20-70% of all cancer cases, often leading to a poor response to standard therapies. Consequently, evaluating KRAS mutation status is critical in customizing the most effective therapy for cancer patients. Current methods for detecting KRAS mutations typically involve a biopsy followed by gene sequencing. However, biopsies carry risks of complications, and the accuracy is sometimes compromised due to tissue sample quality. Hence, there's a pressing demand for noninvasive yet precise ways to assess KRAS mutation status. Now, a novel PET imaging tracer has been proven to safely and effectively detect KRAS for targeted tumor therapy. Early identification of this mutation will allow healthcare professionals to design more effective, personalized treatment strategies.

In this first-in-human study, researchers at Xijing Hospital of Fourth Military Medical University (Xi’an, China) aimed to develop a KRAS-targeted radiotracer and explore its potential in targeting non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). The researchers developed an 18F-PFPMD tracer, based on a KRASG12C inhibitor recently approved by the FDA. They tested its targeting specificity and imaging ability through a series of in vitro and in vivo experiments, as well as further assessments involving healthy volunteers and patients with NSCLC and CRC.

The 18F-PFPMD tracer was obtained with high radiochemical yield, purity, and stability, and demonstrated a selective binding affinity for the KRASG12C protein in preclinical trials. It was also deemed safe for human use, demonstrating quick clearance through the gallbladder and intestines. Notably, in patients with NSCLC and CRC, the tracer accumulated significantly more in tumors harboring the KRASG12C mutation compared to those without, showcasing its potential as a diagnostic tool.

“This research reveals that 18F-PFPMD is a promising molecular imaging tool of significant clinical relevance,” said Jing Wang, MD, PhD, nuclear medicine physician at Xijing Hospital of Fourth Military Medical University. “Moving forward, the tracer could be useful to screen the KRASG12C mutation status, as well as for patient selection of KRASG12C targeted therapy. Moreover, it could be used for monitoring therapeutic response and drug resistance for cancer patients.”

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