Nusrat J Begum1, Anne Thieme2, Nina Eberhardt2, Robert Tauber3, Calogero D'Alessandria2, Ambros J Beer1, Gerhard Glatting1, Matthias Eiber2, Peter Kletting4. 1. Department of Nuclear Medicine, Universität Ulm, Ulm, Germany. 2. Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany; and. 3. Department of Urology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. 4. Department of Nuclear Medicine, Universität Ulm, Ulm, Germany peter.kletting@uniklinik-ulm.de.
Abstract
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.
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.
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