Abstract
Prostate specific membrane antigen (PSMA) has become a major focus point in the research and development of prostate cancer (PCa) imaging and therapeutic strategies using radiolabeled tracers. PSMA has shown to be an excellent target for PCa theranostics because of its high expression on the membrane of PCa cells and the increase in expression during disease progression. Therefore, numerous PSMA-targeting tracers have been developed and (pre)clinically studied with promising results. However, many of these PSMA-targeting tracers show uptake in healthy organs such as the salivary glands, causing radiotoxicity. Furthermore, not all patients respond to PSMA-targeted radionuclide therapy (TRT). This created the necessity of additional preclinical research studies in which existing tracers are reevaluated and new tracers are developed in order to improve PSMA-TRT by protecting the (PSMA-expressing) healthy organs and improving tumor uptake. In this review we will give an overview of the recent preclinical research projects regarding PCa-TRT using PSMA-specific radiotracers, which will give an indication of where the PSMA-TRT research movement is going and what we can expect in future clinical trials.
Highlights
Prostate cancer (PCa) is a major public health problem; approximately 450,000 men have been diagnosed with PCa in Europe in 2018 [1]
Prostate-specific antigen (PSA) level measurements, digital rectal examination, and Gleason score grading are being used for the diagnosis and staging of PCa
Prostate specific membrane antigen (PSMA)-617 and PSMA-I&T are the tracers most often applied to PSMA-targeted radionuclide therapy (TRT) in preclinical research and clinical trials
Summary
Prostate cancer (PCa) is a major public health problem; approximately 450,000 men have been diagnosed with PCa in Europe in 2018 [1]. The overexpression of PSMA on (metastasized) PCa cells makes it an excellent target for imaging and therapy using PSMA-targeting tracers These tracers can be labeled with different varieties of radionuclides for diagnostic (e.g., positron emitter gallium-68) or therapeutic purposes (e.g., beta-particle emitter lutetium-177 or alpha-particle emitter actinium-225). Next to PCa cells, expression of PSMA is found in healthy prostate tissue, the small intestine, central nervous system, proximal renal tubules, and the salivary and lacrimal glands [9,10,11] These PSMA-expressing organs show uptake of almost all PSMA-targeting radiotracers, which might cause toxicity. PSMA-617 and PSMA-I&T are the tracers most often applied to PSMA-TRT in preclinical research and clinical trials Both share the same glu-urea-lys–PSMA binding motif and their DOTA/DOTAGA chelators enable labeling with therapeutic radionuclides [24,25]
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