PT - JOURNAL ARTICLE AU - Begum, Nusrat J. AU - Thieme, Anne AU - Eberhardt, Nina AU - Tauber, Robert AU - D’Alessandria, Calogero AU - Beer, Ambros J. AU - Glatting, Gerhard AU - Eiber, Matthias AU - Kletting, Peter TI - The Effect of Total Tumor Volume on the Biologically Effective Dose to Tumor and Kidneys for <sup>177</sup>Lu-Labeled PSMA Peptides AID - 10.2967/jnumed.117.203505 DP - 2018 Jun 01 TA - Journal of Nuclear Medicine PG - 929--933 VI - 59 IP - 6 4099 - http://jnm.snmjournals.org/content/59/6/929.short 4100 - http://jnm.snmjournals.org/content/59/6/929.full SO - J Nucl Med2018 Jun 01; 59 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&amp;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.