Aim: To simulate the effect of PSMA positive total tumor volume (TTV) on the tumor and organs at risk (OARs) biologically effective doses (BEDs) in patients with metastatic castration resistant prostate cancer (mCRPC) in 177Lu-PSMA radioligand therapy.
Methods: A physiologically-based pharmacokinetic model was fitted to data of 13 patients treated with 177Lu-PSMA I&T. The tumor, kidneys and salivary glands BEDs were simulated for TTVs of 0.1-10 l. The activity and peptide amounts leading to an optimal tumor-to-kidneys BED ratio were also investigated. Results: Increasing the TTV from 0.3 to 3 l, the simulated BEDs for tumor, kidneys, parotid and submandibular glands decreased from (22±15) Gy1.49 to (11.0±6.0) Gy1.49, (6.5±2.3) Gy2.5 to (3.7±1.4) Gy2.5, (10.9±2.7) Gy4.5 to (6.4±1.9) Gy4.5, and (11.0±2.7) Gy4.5 to (6.3±1.9) Gy4.5, respectively. The BED for the red marrow increased from 13 (0.17±0.05) Gy15 to (0.32±0.11) Gy15. For patients with TTV > 0.3 l, the optimal amounts of peptide and activity were (273±136) nmol labeled with (10.4±4.4) GBq.
Conclusion: This simulation study suggests that in patients with large PSMA positive tumor volumes higher activity and peptide amounts could be safely administered to maximize tumor BEDs without exceeding the tolerable BED for the OARs.
Key words: Prostate specific membrane antigen (PSMA); biologically effective dose (BED); total tumor volume (TTV); Physiologically-based pharmacokinetic (PBPK) modeling.