First-Strike Rapid Predictive Dosimetry and Dose Response for ¹⁷⁷Lu-PSMA Therapy in Metastatic Castration-Resistant...

Area of Science:

• Nuclear Medicine
• Medical Physics
• Oncology

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) treatment often relies on empirical dosimetry.
• Personalized predictive dosimetry can optimize radionuclide therapy efficacy and safety.

Purpose of the Study:

• To develop and validate a rapid, personalized predictive dosimetry schema for 177Lu-PSMA-I&T in mCRPC.
• To supersede traditional empiric prescription with clinically meaningful predicted absorbed doses for first-strike optimization.

Main Methods:

• Utilized prostate-specific membrane antigen (PSMA) PET for dosimetric simulation, capturing tumor, marrow, and kidney interplay.
• Integrated radiation principles (fractionation, heterogeneity, dose constraints) into a user-friendly, open-source spreadsheet calculator.
• Sampled tissue radioconcentrations and clinical input for rapid, accurate dosimetry.

Main Results:

• Established a first-strike mean tumor-absorbed dose threshold of >10 Gy for prostate-specific antigen (PSA) response.
• Identified a threshold of ≥20 Gy for hypothetical zero PSA, correlating metastasis-specific dose with PSA decrease.
• Predicted mean first-strike prescription was 11.0 ± 4.0 GBq, constrained by marrow dose rate.

Conclusions:

• The rapid schema is feasible for real-world theranostics units, exceeding current best practices.
• Dosimetric thresholds and predictive parameters rationalize patient-specific prescriptions.
• The framework can be applied to other systemic radionuclide therapies.