Kidney Doses in 177Lu-Based Radioligand Therapy in Prostate Cancer: Is Dose Estimation Based on Reduced Dosimetry Measurements Feasible?

Abstract

The radiation dose to the kidneys should be monitored in prostate cancer patients treated with radioligand therapy (RLT) targeting the prostate-specific membrane antigen (PSMA). We analyzed whether pretherapeutic kidney function is predictive of subsequent kidney dose and to what extent the cumulative kidney dose at the end of multiple therapy cycles can be predicted from a dosimetry based on the first cycle. Methods: Data of 59 patients treated with at least 2 cycles of 177Lu-PSMA-617 (PSMA RLT) were analyzed. Treatment (median, 6 GBq/cycle) was performed at 6- to 8-wk intervals, accompanied by voxel-based 3-dimensional dosimetry (measured kidney dose) with SPECT/CT on each of days 0-3 and once during days 6-9. Pretherapeutic kidney function (estimated glomerular filtration rate, mercaptoacetyltriglycine clearance) was correlated to the kidney doses. Cumulative kidney doses at the end of treatment were compared with a dose estimated from the population-based mean kidney dose, individual first-cycle kidney dose, and mean kidney doses of cycles 1, 3, and 5 per administered activity. Results: In total, 176 PSMA RLT cycles were performed, with a median of 3 cycles per patient. The average kidney dose per administered activity of all 176 cycles was 0.67 ± 0.24 Gy/GBq (range, 0.21-1.60 Gy/GBq). Mercaptoacetyltriglycine clearance and estimated glomerular filtration rate were no reliable predictors of subsequent absorbed kidney dose and showed only small effect sizes (R 2 = 0.080 and 0.014 [P = 0.039 and 0.375], respectively). All simplified estimations of cumulative kidney dose correlated significantly (P < 0.001) with measured kidney doses: estimations based on the individual first-cycle dose were more accurate than the use of the population-based average kidney dose (R 2 = 0.853 vs. 0.560). Dose estimation was best when the doses of cycles 3 and 5 were included as well (R 2 = 0.960). Conclusion: Pretherapeutic renal function was not predictive of subsequent kidney dose during therapy. Extrapolation of individual data from dosimetry of the first cycle was highly predictive of the cumulative kidney dose at the end of treatment. This prediction was further improved by the integration of dose information from every other cycle. In any case, because of a high interindividual variance, an individual dosimetry is advisable.