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|Title:||Targeted alpha therapy of mCRPC: Dosimetry estimate of 213Bismuth-PSMA-617|
|Authors:||KRATOCHWIL CLEMENS; SCHMIDT K.; AFSHAR-OROMIEH ALI; BRUCHERTSEIFER FRANK; RATHKE H; MORGENSTERN ALFRED; HABERKORN UWE; GIESEL FREDERIK|
|Citation:||EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING vol. 45 no. 1 p. 31-37|
|Type:||Articles in periodicals and books|
|Abstract:||Purpose: 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. Methods: Three patients with metastatic prostate cancer underwent PET-scans 0.1h, 1h, 2h, 3h, 4h and 5h 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 data for 225Ac-PSMA-617. Results: Assuming a relative biological effectiveness of 5 for alpha-radiation, the dosimetry estimate revealed mean doses of 8.1 Sv/GBq for salivary glands, 8.1 Sv/GBq for kidneys and 0.52 Sv/GBq for red-marrow. Liver (1.2 Sv/GBq), spleen (1.4 Sv/GBq), bladder (0.28 Sv/GBq) and other organs (0.26 Sv/GBq) were not dose-limiting. Effective dose is 0.56 Sv/GBq. Tumor lesions were in the range 3.2-9.0 Sv/GBq (median 7.6 Sv/GBq). Kidneys would limit the cumulative dose to 3.7 GBq; red marrow might limit the maximum single dose to 2 GBq. Three cycles of 1.2 GBq 213Bi-PSMA-617 present a reasonable fractionation regime. Despite promising, the therapeutic index was inferior compared to 225Ac-PSMA-617. Conclusions: 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 longer biological half-life of PSMA-617 in dose limiting organs than physical half-life of 213Bi, degrading this nuclide as a second choice radiolabel for targeting alpha therapy of prostate cancer.|
|JRC Directorate:||Nuclear Safety and Security|
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