Radionuclides landscape in prostate cancer theranostics

Prostate cancer, a malignancy of significant prevalence, affects approximately half a million men in Europe, with one in twelve males receiving a diagnosis before reaching the age of 75. Radiotheranostics represents a paradigm shift in prostate cancer treatment, leveraging radionuclides for diagnostic and therapeutic applications, with PSMA emerging as the primary molecular target. Regulatory bodies have approved various PSMA-targeted radiodiagnostic agents, such as [¹⁸F]DCFPyL (PYLARIFY®, Lantheus Holdings), [¹⁸F]rhPSMA-7.3 (POSLUMA®, Blue Earth Diagnostics), and [⁶⁸Ga]Ga-PSMA-11 (LOCAMETZ®, Novartis/ILLUCCIX®, Telix Pharmaceuticals), as well as therapeutic agents like [¹⁷⁷Lu]Lu-PSMA-617 (PLUVICTO®, 15 Novartis). The approval of PLUVICTO® in March 2022 for patients with metastatic castration-resistant prostate cancer who have undergone prior treatments, including androgen receptor pathway-targeting agents and taxane-based chemotherapy, represents a significant advancement. Other radionuclides like ¹⁶¹Tb, ¹⁴⁹Tb, ²²⁵Ac, ²²⁷Th, ²²³Ra, ²¹¹At, ²¹³ Bi, ²¹²Pb, ⁸⁹Zr, and ¹²⁵I are presented, emphasizing their clinical implementation or the stage of clinical trial they are in in the flow to biomedical implementation. Three clinically wise used radionuclides ¹⁷⁷Lu, ²²⁵Ac, ²²³Ra are shown along with their characteristics. This review aims to elucidate the molecular mechanisms underpinning PSMA, explore the clinical applications of PSMA-targeted radiotheranostics, and critically examine the diverse challenges these therapies encounter in the treatment of prostate cancer.