First-Strike Rapid Predictive Dosimetry and Dose Response for177Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer

We devised and clinically validated a schema of rapid personalized predictive dosimetry for 177Lu-PSMA-I its threshold to achieve hypothetical zero PSA was 20 Gy or more. Each patient's PSA doubling time can be used to personalize their unique absorbed dose–response threshold. The predicted mean first-strike prescription constrained by marrow-absorbed dose rate per fraction was 11.0 ± 4.0 GBq. Highly favorable conditions (tumor sink effect) were dosimetrically expressed as the combination of tumor–to–normal-organ ratios of more than 150 for marrow and more than 4 for kidney. Our schema obviates the traditional role of the SUV as a predictive parameter. Conclusion: Our rapid schema is feasible to implement in any busy real-world theranostics unit and exceeds today's best practice standards. Our dosimetric thresholds and predictive parameters can radiobiologically rationalize each patient's first-strike prescription down to a single becquerel. Favorable tumor–to–normal-organ ratios can be prospectively exploited by predictive dosimetry to optimize the first-strike prescription. The scientific framework of our schema may be applied to other systemic radionuclide therapies.