PSMA Targeted Molecular Imaging and Radioligand Therapy for Prostate Cancer: Optimal Patient and Treatment Issues

Abstract

Theranostics (therapy + diagnosis) targeting prostate-specific membrane antigen (PSMA) is an emerging therapeutic modality that could alter treatment strategies for prostate cancer. Although PSMA-targeted radioligand therapy (PSMA-RLT) has a highly therapeutic effect on PSMA-positive tumor tissue, the efficacy of PSMA-RLT depends on PSMA expression. Moreover, predictors of treatment response other than PSMA expression are under investigation. Therefore, the optimal patient population for PSMA-RLT remains unclear. This review provides an overview of the current status of theranostics for prostate cancer, focusing on PSMA ligands. In addition, we summarize various findings regarding the efficacy and problems of PSMA-RLT and discuss the optimal patient for PSMA-RLT.

Structure-activity relationship study of mesyl and busyl phosphoramidate antisense oligonucleotides for unaided and PSMA-mediated uptake into prostate cancer cells

“…We selected two variants of PSMA ligands, namely, MA-257 and MA-415 ( Supplementary Figure S2 ), which were validated in previous works ( Machulkin et al, 2019 ; Machulkin et al, 2021 ). MA-415 is an azido derivative of the most common PSMA ligand that was clinically validated for radiotherapy ( Machulkin et al, 2019 ; Hoshi et al, 2023 ). The key point of the more advanced MA-257 ligand is a linker bearing a set of aromatic residues that improves binding to the PSMA receptor due to hydrophobic interactions with the channel ( Machulkin et al, 2021 ).…”

“…In several clinical studies PSMA ligands showed good results for the delivery of diagnostic and therapeutic agents ( Wu et al, 2011 ; Barve et al, 2014 ; Wang et al, 2021 ). Also, radioisotope labeled PSMA ligands were applied for a diagnostical PSMA-based PET imaging, and in 2022 FDA approved a radiopharmaceutical 177 Lu-PSMA-617 to treat PCa ( Hoshi et al, 2023 ).…”

Two Novel [68Ga]Ga-Labeled Radiotracers Based on Metabolically Stable [Sar11]RM26 Antagonistic Peptide for Diagnostic Positron Emission Tomography Imaging of GRPR-Positive Prostate Cancer

“…Thus, high and specific binding to their biomolecular targets and a stable in vivo complexation of the radiometal utilized are of the outmost importance. Two of the most commonly used biomolecules serving as targets for radiopharmaceutical development for Pca are prostate specific membrane antigen (PSMA) and gastrin releasing peptide receptor (GRPR). − Over the past years, PSMA was recognized as clinically relevant biomolecular-target in management of PCa, with the first FDA approved radiopharmaceuticals designed for diagnosis and therapy being PSMA-targeting radioligands (LOCAMETZ, Pluvicto for imaging and therapy, respectively). − It is known that PSMA expression in PCa is strongly associated with later stages of the disease, while in the early stages of the malignancy, its expression is rather low. − …”

“…9 − 11 Over the past years, PSMA was recognized as clinically relevant biomolecular-target in management of PCa, with the first FDA approved radiopharmaceuticals designed for diagnosis and therapy being PSMA-targeting radioligands (LOCAMETZ, Pluvicto for imaging and therapy, respectively). 12 − 14 It is known that PSMA expression in PCa is strongly associated with later stages of the disease, while in the early stages of the malignancy, its expression is rather low. 12 − 14 …”

“… 12 − 14 It is known that PSMA expression in PCa is strongly associated with later stages of the disease, while in the early stages of the malignancy, its expression is rather low. 12 − 14 …”