RT Journal Article SR Electronic T1 Prediction of Resistance to 177Lu-PSMA Therapy by Assessment of Baseline Circulating Tumor DNA Biomarkers JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1721 OP 1725 DO 10.2967/jnumed.123.266167 VO 64 IS 11 A1 Sartor, Oliver A1 Ledet, Elisa A1 Huang, Minqui A1 Schwartz, Jennifer A1 Lieberman, Alex A1 Lewis, Brian A1 Layton, Jodi A1 Barata, Pedro A1 Jang, Albert A1 Hawkins, Madeline A1 Pocha, Olivia A1 Lanka, Sree A1 Harris, Kendra YR 2023 UL http://jnm.snmjournals.org/content/64/11/1721.abstract AB 177Lu-PSMA-617 and 177Lu-PSMA I&T (collectively termed 177Lu-PSMA) are currently being used for the treatment of selected metastatic castration-resistant prostate cancer (mCRPC) patients with PSMA PET–positive disease, but biomarkers for these agents remain incompletely understood. Methods: Pretreatment circulating tumor DNA (ctDNA) samples were collected from 44 mCRPC patients receiving 177Lu-PSMA treatment. Prostate-specific antigen responders and nonresponders were assessed relative to the ctDNA findings at baseline. Results: The ctDNA findings indicated that nonresponders were more likely to have gene amplifications than were responders (75% vs. 39.2%, P = 0.03). In particular, amplifications in FGFR1 (25% vs. 0%, P = 0.01) and CCNE1 (31.2% vs. 0%, P = 0.001) were more likely to be present in nonresponders. CDK12 mutations were more likely to be present in nonresponders (25% vs. 3.6%, P = 0.05). Conclusion: Our analyses indicate that ctDNA assays may contain specific biomarkers predictive of response or resistance for 177Lu-PSMA–treated mCRPC patients. Additional confirmatory studies are required before clinicians can use these findings to make personalized treatment decisions.