Chapter 10: Prostate-specific Membrane Antigen Targeted Prostate Imaging and Therapy Check Access

Prostate cancer (PCa) is the second most prevalent malignancy in the world. Nuclear medicine plays a pivotal role in the management of patients with PCa. The excellent results of the OSPREY, CONDOR and ProPSMA trials paved the way for the Food and Drug Administration (FDA) approval of 2-(3-{1-carboxy-5-[(6-[¹⁸F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyl) and [⁶⁸Ga]Ga–N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid (HBED-cc)–prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET) agents for diagnostic use in PCa. The VISION trial showed the success of [¹⁷⁷Lu]Lu–1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)–PSMA-617 targeted therapy in improving the progression-free and overall survival in metastatic castration-resistant PCa, leading to its FDA approval in 2022. The theranostic approach involves targeting a transmembrane (Type II) receptor comprising two small domains of 19 amino acids (intracellular) and 24 amino acids (transmembrane) and a large extracellular domain of 707 amino acids. PSMA exhibits overexpression in PCa. Consequently, radiolabeled PSMA ligands (antibodies or peptides) using various radionuclides (¹¹¹In, ^99mTc, ⁶⁸Ga, ¹⁸F, ⁸⁹Zr, ¹⁷⁷Lu, ²²⁵Ac) serve a dual purpose, the diagnosis and therapy of primary and metastatic PCa. In this chapter, the fundamental radiochemistry, biodistribution patterns, dosimetry and clinical applications of radiopharmaceuticals are explained in detail.