RT Journal Article SR Electronic T1 The Effect of Total Tumor Volume on the Biologically Effective Dose to Tumor and Kidneys for 177Lu-Labeled PSMA Peptides JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 929 OP 933 DO 10.2967/jnumed.117.203505 VO 59 IS 6 A1 Begum, Nusrat J. A1 Thieme, Anne A1 Eberhardt, Nina A1 Tauber, Robert A1 D’Alessandria, Calogero A1 Beer, Ambros J. A1 Glatting, Gerhard A1 Eiber, Matthias A1 Kletting, Peter YR 2018 UL http://jnm.snmjournals.org/content/59/6/929.abstract AB 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 177Lu-PSMA radioligand therapy. Methods: A physiologically based pharmacokinetic model was fitted to the data of 13 patients treated with 177Lu-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 ± 15 to 11.0 ± 6.0 Gy1.49, 6.5 ± 2.3 to 3.7 ± 1.4 Gy2.5, 11.0 ± 2.7 to 6.4 ± 1.9 Gy4.5, and 10.9 ± 2.7 to 6.3 ± 1.9 Gy4.5, respectively (where the subscripts denote that an α/β 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 ± 0.05 to 0.32 ± 0.11 Gy15. For patients with a TTV of more than 0.3 L, the optimal amount of peptide was 273 ± 136 nmol and the optimal activity was 10.4 ± 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.