@article {Begum929, author = {Nusrat J. Begum and Anne Thieme and Nina Eberhardt and Robert Tauber and Calogero D{\textquoteright}Alessandria and Ambros J. Beer and Gerhard Glatting and Matthias Eiber and Peter Kletting}, title = {The Effect of Total Tumor Volume on the Biologically Effective Dose to Tumor and Kidneys for 177Lu-Labeled PSMA Peptides}, volume = {59}, number = {6}, pages = {929--933}, year = {2018}, doi = {10.2967/jnumed.117.203505}, publisher = {Society of Nuclear Medicine}, abstract = {The aim of this work was to simulate the effect of prostate-specific membrane antigen (PSMA){\textendash}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{\textendash}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 {\textpm} 15 to 11.0 {\textpm} 6.0 Gy1.49, 6.5 {\textpm} 2.3 to 3.7 {\textpm} 1.4 Gy2.5, 11.0 {\textpm} 2.7 to 6.4 {\textpm} 1.9 Gy4.5, and 10.9 {\textpm} 2.7 to 6.3 {\textpm} 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 {\textpm} 0.05 to 0.32 {\textpm} 0.11 Gy15. For patients with a TTV of more than 0.3 L, the optimal amount of peptide was 273 {\textpm} 136 nmol and the optimal activity was 10.4 {\textpm} 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.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/59/6/929}, eprint = {https://jnm.snmjournals.org/content/59/6/929.full.pdf}, journal = {Journal of Nuclear Medicine} }