The effect of total tumor volume on the biologically effective dose to tumor and kidneys for ¹⁷⁷ Lu-Labeled PSMA peptides

The aim of this work was to simulate the effect of prostate-specific membrane antigen (PSMA)–positive total tumor volume (TTV) on the biologically effective doses (BEDs) to tumors and organs at risk in patients with metastatic castration-resistant prostate cancer who are undergoing ¹⁷⁷ Lu-PSMA radioligand therapy. Methods: A physiologically based pharmacokinetic model was fitted to the data of 13 patients treated with ¹⁷⁷ Lu-PSMA I&T (a PSMA inhibitor for imaging and therapy). The tumor, kidney, and salivary gland 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: When the TTV was increased from 0.3 to 3 L, the simulated BEDs to tumors, kidneys, parotid glands, and submandibular glands decreased from 22 6 15 to 11.0 6 6.0 Gy _1.49 , 6.5 6 2.3 to 3.7 6 1.4 Gy _2.5 , 11.0 6 2.7 to 6.4 6 1.9 Gy _4.5 , and 10.9 6 2.7 to 6.3 6 1.9 Gy _4.5 , respectively (where the subscripts denote that an a/b of 1.49, 2.5, or 4.5 Gy was used to calculate the BED). The BED to the red marrow increased from 0.17 6 0.05 to 0.32 6 0.11 Gy ₁₅ . For patients with a TTV of more than 0.3 L, the optimal amount of peptide was 273 6 136 nmol and the optimal activity was 10.4 6 4.4 GBq. Conclusion: This simulation study suggests that in patients with large PSMA-positive tumor volumes, higher activities and peptide amounts can be safely administered to maximize tumor BEDs without exceeding the tolerable BED to the organs at risk.