Targeted alpha therapy of mCRPC

• Verfasst von: Kratochwil, Clemens [VerfasserIn]
• Verfasst von: Afshar-Oromieh, Ali [VerfasserIn]
• Verfasst von: Rathke, Hendrik [VerfasserIn]
• Verfasst von: Haberkorn, Uwe [VerfasserIn]
• Verfasst von: Giesel, Frederik L. [VerfasserIn]
• Titel: Targeted alpha therapy of mCRPC
• Titelzusatz: dosimetry estimate of 213Bismuth-PSMA-617
• Verf.angabe: Clemens Kratochwil, Karl Schmidt, Ali Afshar-Oromieh, Frank Bruchertseifer, Hendrik Rathke, Alfred Morgenstern, Uwe Haberkorn, Frederik L. Giesel
• Jahr: 2018
• Jahr des Originals: 2017
• Umfang: 7 S.
• Teil: volume:45
• Teil: year:2018
• Teil: number:1
• Teil: pages:31-37
• Teil: extent:7
• Fussnoten: First online: 11 September 2017 ; Im Titel ist die Zahl "213" hochgestellt ; Gesehen am HDHB/25.10.2018
• Titel Quelle: Enthalten in: European journal of nuclear medicine and molecular imaging
• Ort Quelle: Heidelberg [u.a.] : Springer-Verl., 2002
• Jahr Quelle: 2018
• Band/Heft Quelle: 45(2018), 1, Seite 31-37
• ISSN Quelle: 1619-7089
• DOI: doi:10.1007/s00259-017-3817-y
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Bi-213
• Sach-SW: Prostate cancer
• Sach-SW: PSMA
• Sach-SW: Targeting alpha therapy
• K10plus-PPN: 1582288062

Abstract

PurposePSMA-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.MethodsThree 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.ResultsAssuming 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 SvRBE5/GBq) were not dose-limiting. The effective dose is 0.56 Sv RBE5/GBq. Tumor lesions were in the range 3.2-9.0 SvRBE5/GBq (median 7.6 SvRBE5/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.ConclusionsDosimetry 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.