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

Abstract

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.

The 68Ga/177Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUVmax values and absorbed dose estimates

“…Kratochwil et al [30] also found 50% decreased SUV max values but no attempt to correlate them with absorbed dose calculation was made. In line with our data, in a very recent study, Okamoto et al [33] also report only moderate correlation of pre-therapeutic SUVs with absorbed dose estimates using a PSMA inhibitor for imaging and therapy (PSMA I&T). Obviously, besides target expression, also other factors of tumour biology are present which determine therapy response.…”

Combined model-based and patient-specific dosimetry for 18F-DCFPyL, a PSMA-targeted PET agent

“…Herrmann et al [39] found that the AD values for the SG are lower than those for the spleen. Physiological uptake in the LG and the SG has been observed in recent radionuclide therapy studies using 177 Lu-PSMA-I&T [41] and 177 Lu-DKFZ-PSMA-617 [42]. The kidneys and the LG were found to be the organs receiving the highest AD, respectively, in these studies.…”

Biodistribution and radiation dosimetry of [64Cu]copper dichloride: first-in-human study in healthy volunteers

“…The same applies to other radiosensitive organs and tissues such as gonads and red bone marrow. Note from Table 4 that the effective doses of [ 64 Cu]CuCl 2 are similar to those estimated for 177 Lu-PSMA, a typical agent used in TRNT [19]. However, the absorbed doses to normal organs are considerably higher for 177 Lu-PSMA than those of [ 64 Cu]CuCl 2 .…”