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.

Keywords: PSMA ligands; PSMA-targeted radioimmunoconjugates; prostate cell-surface receptors; prostate targeted therapy.

Figure 1

Schematic structure of selected prostate cell membrane receptors as potential prostate cancer therapy targets.

Figure 2

Schematic representation of antibody-based molecules. VH—heavy chain variable region, VL—light-chain variable region, CL—light-chain constant region, CH—high chain constant region 1, CH2—high chain constant region 2. CH3—high chain constant region 3.

Figure 3

Chemical structure of selected PSMA-targeted small-molecule inhibitors. (A) urea-based compounds, (B) glutamatephosphoramidates, (C) 2-(phosphinylmethyl)pentanedioic acids, (D) PSMA-617, (E) MIP-1072, (F) MIP-1095, (G) PSMA I&T.

Figure 4

Schematic representation of the tissue-penetration range and density of ionization events caused by β⁻-particles, α-particles, and Auger electrons.