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

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 (213)Bi. METHODS: Three patients with metastatic prostate cancer underwent PET scans 0.1 h, 1 h, 2 h, 3 h, 4...

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Detalles Bibliográficos
Autores principales: Kratochwil, Clemens, Schmidt, Karl, Afshar-Oromieh, Ali, Bruchertseifer, Frank, Rathke, Hendrik, Morgenstern, Alfred, Haberkorn, Uwe, Giesel, Frederik L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700223/
https://www.ncbi.nlm.nih.gov/pubmed/28891033
http://dx.doi.org/10.1007/s00259-017-3817-y
Descripción
Sumario: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 (213)Bi. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00259-017-3817-y) contains supplementary material, which is available to authorized users.

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