Radiation Dosimetry for¹⁷⁷Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy is increasingly used in metastatic castration-resistant prostate cancer. We aimed to estimate the absorbed doses for normal organs and tumor lesions using 177 Lu-PSMA I&T (I&T is imaging and therapy) in patients undergoing up to 4 cycles of radioligand therapy. Results were compared with pretherapeutic Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBEDCC)] ( 68 Ga-PSMA-HBED-CC) PET. Methods: A total of 34 cycles in 18 patients were analyzed retrospectively. In 15 patients the first, in 9 the second, in 5 the third, and in 5 the fourth cycle was analyzed, respectively. Whole-body scintigraphy was performed at least between 30-120 min, 24 h, and 6-8 d after administration. Regions of interest covering the whole body, organs, and up to 4 tumor lesions were drawn. Organ and tumor masses were derived from pretherapeutic 68 Ga-PSMA-HBED-CC PET/CT. Absorbed doses for individual cycles were calculated using OLINDA/EXM. SUVs from pretherapeutic PET were compared with absorbed doses and with change of SUV. Results: The mean whole-body effective dose for all cycles was 0.06 6 0.03 Sv/GBq. The mean absorbed organ doses were 0.72 6 0.21 Gy/GBq for the kidneys; 0.12 6 0.06 Gy/GBq for the liver; and 0.55 6 0.14 Gy/GBq for the parotid, 0.64 6 0.40 Gy/ GBq for the submandibular, and 3.8 6 1.4 Gy/GBq for the lacrimal glands. Absorbed organ doses were relatively constant among the 4 different cycles. Tumor lesions received a mean absorbed dose per cycle of 3.2 6 2.6 Gy/GBq (range, 0.22-12 Gy/GBq). Doses to tumor lesions gradually decreased, with 3.5 6 2.9 Gy/GBq for the first, 3.3 6 2.5 Gy/GBq for the second, 2.7 6 2.3 Gy/GBq for the third, and 2.4 6 2.2 Gy/GBq for the fourth cycle. SUVs of pretherapeutic PET moderately correlated with absorbed dose (r 5 0.44, P , 0.001 for SUV max ; r 5 0.43, P , 0.001 for SUV mean ) and moderately correlated with the change of SUV (r 5 0.478, P , 0.001 for SUV max , and r 5 0.50, P , 0.001 for SUV mean ). Conclusion: Organ-and tumorabsorbed doses for 177 Lu-PSMA I&T are comparable to recent reports and complement these with information on an excellent correlation between the 4 therapy cycles. With the kidneys representing the critical organ, a cumulative activity of 40 GBq of 177 Lu-PSMA I&T appears to be safe and justifiable. The correlation between pretherapeutic SUV and absorbed tumor dose emphasizes the need for PSMA-ligand PET imaging for patient selection.