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 ²¹³Bi.

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 ⁶⁸Ga-PSMA-617. Source organs were kidneys, liver, spleen, salivary glands, bladder, red marrow and representative tumor lesions. The imaging nuclide ⁶⁸Ga was extrapolated to the half-life of ²¹³Bi. The residence times of ²¹³Bi were forwarded to the instable daughter nuclides. OLINDA was used for dosimetry calculation. Results are discussed in comparison to literature data for ²²⁵Ac-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 ²²⁵Ac-PSMA-617.

Dosimetry of ²¹³Bi-PSMA-617 is in a range traditionally considered reasonable for clinical application. Nevertheless, compared to ²²⁵Ac-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 ²¹³Bi, rendering this nuclide as a second choice radiolabel for targeted alpha therapy of prostate cancer.