Targeted alfa particle therapy with 225Ac-Psma-617

April 2, 2019, 11:15 409

 

According to statistical research, there are currently over 1 million patients suffering from prostate cancer over the world. About 6.7% of men died in prostate cancer during the year.

Recently, targeted radionuclide therapy in the treatment of prostate cancer has gained wide scope in the world of nuclear medicine.

Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. A number of peptide-containing radionuclide carrier antibodies (PSMA-617, PSMA-11, PSMA-1007 and others.) have been successfully synthesized by experts and are successfully used for the diagnostics and treatment of prostate cancer in nuclear medicine. 

In targeted radionuclide therapy, the biological effect is obtained by energy absorbed from the radiation emitted by the radionuclide. Whereas the radionuclides used for nuclear medicine imaging emit gamma rays, which can penetrate deeply into the body, the radionuclides used for targeted radionuclide therapy must emit radiation with a relatively short path length. There are three types of particulate radiation of consequence for targeted radionuclide therapy -beta particles, alpha particles and Auger electrons which can irradiate tissue volumes with multicellular, cellular and subcellular dimensions respectively.

 

FIGURE 4.3. Penetrating power of alpha and beta particles.

Alpha-particle-emitters are of considerable interest for radioimmunotherapy applications because of the high linear energy transfer (LET) and short range of alpha particles in tissue (a few cell diameters) A single atom of an alpha-emitting isotope is capable of killing a tumor cell, making it among the most potent cytotoxic agents available. The short range of the alpha particle increases its safety profile because nonspecific irradiation of normal tissue around the target cells is greatly reduced or absent.

 

The high alpha particle LET is on the order of 100 keV/μm and it can produce substantially more lethal double-strand DNA breaks per alpha track than beta particles when traversing a cell nucleus. The alpha particle tracks are relatively short and thus have a limited range in tissue (on the order of a few cell diameters). This confines the toxic effect to a relatively small field - within a few cell diameters from the site of decay versus the much longer-ranged beta particles.

225Ac radionuclide carrier radiopharmaceuticals (225Ac-PSMA-617) have recently become of great interest in nuclear medicine in the treatment of radionuclide target-therapy. 225Ac is the parent radionuclide of 213Bi and has been proposed as a potentially useful therapeutic radionuclide. It has a 10 d half-life and nets 4 alpha particles per decay. 225Ac-PSMA-617 was offered as salvage therapy in accordance with paragraph 37, “Unproven Interventions in Clinical Practice,” of the updated Declaration of Helsinki, which include priority of approved treatments and confirmation of the indication by a nuclear medicine physician and an expert in urologic oncology.

 

FIGURE 1.

Pretherapeutic tumor spread (A), restaging 2 mo after third cycle of 225Ac-PSMA-617 (B), and restaging 2 mo after one additional consolidation therapy (C). 

                                                                                                                                                                                                                                                                          By Shukurov R. 

References:

  1. 225Ac-PSMA-617 for PSMA-Targeted a-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer Clemens Kratochwil*1, Frank Bruchertseifer*2, Frederik L. Giesel1, Mirjam Weis2, Frederik A. Verburg3, Felix Mottaghy3, Klaus Kopka4, Christos Apostolidis2, Uwe Haberkorn1, and Alfred Morgenstern2

  2. Design and synthesis of 225Ac radioimmunopharmaceuticals Michael R. McDevitta, Dangshe Maa, Jim Simonb, R. Keith Frankb, David A. Scheinberga,*,1a Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

  3.    Report Technical Meeting on "Alpha emitting radionuclides and radiopharmaceuticals for therapy" June, 24−28, 2013 IAEA Headquarters, Vienna, Austria  

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