A study in the July issue of The Journal of Nuclear Medicine reports that circulating tumor DNA (ctDNA) profiling could help select patients likely to benefit from radium-223 (^223Ra) radiopharmaceutical therapy in metastatic castration-resistant prostate cancer (mCRPC). The research suggests ctDNA can flag which patients are more likely to respond, moving toward biomarker-driven patient selection for radiopharmaceutical treatment rather than treating based on clinicopathologic factors alone. If replicated, ctDNA selection could improve therapeutic efficiency and reduce exposure to ineffective regimens in a setting where treatment sequencing decisions are especially consequential.