Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

Abstract

Prostate cancer is the most commonly diagnosed malignancy in men and the second leading cause of cancer-related deaths in Western civilization. Although localized prostate cancer can be treated effectively in different ways, almost all patients progress to the incurable metastatic castration-resistant prostate cancer. Due to the significant mortality and morbidity rate associated with the progression of this disease, there is an urgent need for new and targeted treatments. In this review, we summarize the recent advances in research on identification of prostate tissue-specific antigens for targeted therapy, generation of highly specific and selective molecules targeting these antigens, availability of therapeutic radionuclides for widespread medical applications, and recent achievements in the development of new-generation small-molecule inhibitors and antibody-based strategies for targeted prostate cancer therapy with alpha-, beta-, and Auger electron-emitting radionuclides.

Preclinical and Clinical Status of PSMA-Targeted Alpha Therapy for Metastatic Castration-Resistant Prostate Cancer

“…Targeted radionuclide therapy (TRT) is a rapidly growing treatment modality for mCRPC [ 33 , 55 , 56 ]. TRT involves the use of radioisotopes or radiolabeled compounds that either naturally accumulate in or are designed to target and deliver a cytotoxic amount of radiation to prostate cancer cells sparing the surrounding normal tissues [ 55 , 56 ].…”

“…Targeted radionuclide therapy (TRT) is a rapidly growing treatment modality for mCRPC [ 33 , 55 , 56 ]. TRT involves the use of radioisotopes or radiolabeled compounds that either naturally accumulate in or are designed to target and deliver a cytotoxic amount of radiation to prostate cancer cells sparing the surrounding normal tissues [ 55 , 56 ]. The systemic administration of tumor-targeted radiopharmaceuticals allows the simultaneous treatment of wide-spread bone and extraskeletal metastases [ 56 , 57 ], whereas a multiple and large-field irradiation using external beam radiotherapy is too toxic [ 58 ].…”

“…Overview of α-emitting radionuclides used in PSMA-TAT[71][72][73][74][75]. Comparisons of prostate-specific membrane antigen (PSMA)-targeting small molecules, antibodies, and their fragments[55,[76][77][78][79][80].…”

Progress in Delivery of siRNA-Based Therapeutics Employing Nano-Vehicles for Treatment of Prostate Cancer

“…PCa affects 30% of men over 50 years of age with only 10% of cases showing clinically significant symptoms [ 5 ]. Surgery, radiotherapy, chemotherapy, and hormone therapy are common therapeutic strategies in PCa therapy [ 6 ]. When PCa recurrence occurs or when patients with PCa are diagnosed with advanced stages, main therapy becomes androgen ablation using luteinizing hormone releasing hormone (LHRH) agonists and antagonists and/or anti-androgen receptors (ARs) [ 7 , 8 ].…”

Engineered Fragments of the PSMA-Specific 5D3 Antibody and Their Functional Characterization

“…Prostate-specific membrane antigen (PSMA) is one of the leading PCa-specific biomarkers strongly expressed on PCa cells [15]. The specific presence of PSMA in primary, high-grade, androgen-independent, and metastatic PCa tumors predetermines the enzyme as a prime tool for PCa imaging and therapy [16][17][18][19]. Consequently, PSMA-specific antibodies are being developed as new PCa-targeting theranostics.…”