Targeted alpha therapy of mCRPC: Dosimetry estimate of 213Bismuth-PSMA-617

PSMA-617 is a small molecule targeting the prostate-specific membrane antigen (PSMA). In this work, we estimate the radiation dosimetry for this ligand labeled with the alpha-emitter 213 Bi. Three patients with metastatic prostate cancer underwent PET scans 0.1 h, 1 h, 2 h, 3 h, 4 h and 5 h after injection of 68 Ga-PSMA-617. Source organs were kidneys, liver, spleen, salivary glands, bladder, red marrow and representative tumor lesions. The imaging nuclide 68 Ga was extrapolated to the half-life of 213 Bi. The residence times of 213 Bi were forwarded to the instable daughter nuclides. OLINDA was used for dosimetry calculation. Results are discussed in comparison to literature data for 225 Ac-PSMA-617. Assuming a relative biological effectiveness of 5 for alpha radiation, the dosimetry estimate revealed equivalent doses of mean 8.1 Sv RBE5 /GBq for salivary glands, 8.1 Sv RBE5 /GBq for kidneys and 0.52 Sv RBE5 /GBq for red marrow. Liver (1.2 Sv RBE5 /GBq), spleen (1.4 Sv RBE5 /GBq), bladder (0.28 Sv RBE5 /GBq) and other organs (0.26 Sv RBE5 /GBq) were not dose-limiting. The effective dose is 0.56 Sv RBE5 /GBq. Tumor lesions were in the range 3.2–9.0 Sv RBE5 /GBq (median 7.6 Sv RBE5 /GBq). Kidneys would limit the cumulative treatment activity to 3.7 GBq; red marrow might limit the maximum single fraction to 2 GBq. Despite promising results, the therapeutic index was inferior compared to 225 Ac-PSMA-617. Dosimetry of 213 Bi-PSMA-617 is in a range traditionally considered reasonable for clinical application. Nevertheless, compared to 225 Ac-PSMA-617, it suffers from higher perfusion-dependent off-target radiation and a longer biological half-life of PSMA-617 in dose-limiting organs than the physical half-life of 213 Bi, rendering this nuclide as a second choice radiolabel for targeted alpha therapy of prostate cancer.