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Review
. 2025 Jul 28;13(8):1837.
doi: 10.3390/biomedicines13081837.

PSMA-Directed Theranostics in Prostate Cancer

Salman Ayub Jajja  1 , Nandini Sodhi  2 , Ephraim E Parent  3 , Parminder Singh  4
Affiliations
Review

PSMA-Directed Theranostics in Prostate Cancer

Salman Ayub Jajja et al. Biomedicines. .

Abstract

Following lung cancer, prostate cancer is the leading cause of cancer death in men. High-risk localized tumor burden or metastatic disease often progresses, refractory to initial treatment regimens. There is ongoing development of technology to appropriately identify high-risk patients, stage them correctly, and offer appropriate treatments to obtain the best clinical outcomes. Prostate cancer-specific membrane antigen (PSMA) is a transmembrane glutamate carboxypeptidase, which helps regulate folate absorption, and its overexpression is pathologically directly proportional and associated with prostate cancer. Increased PSMA expression is a known independent risk factor for poorer survival, and most metastatic lesions in CRPC are PSMA positive. Over the last decade, several PSMA-based PET radiopharmaceuticals have demonstrated superior sensitivities and specificities compared to traditional imaging methods. These outcomes have been demonstrated by several large clinical trials. As the data emerges, these diagnostics are being integrated into standard of care protocol to facilitate nuanced identification of malignant lesions. PSMA is also being targeted through several therapeutics, including radioligands and immunotherapies such as CAR-T, BiTEs, and ADCs. This review will discuss the landscape of PSMA-based theranostics in the context of prostate cancer.

Keywords: PSMA theranostics; antibody drug conjugates; immunotherapy in prostate cancer; prostate cancer therapeutics; radioligand therapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Cartoon representation of PSMA’s structure [7].
Figure 2
Figure 2
Comparison of 18F-rhPSMA-7.3 imaging to PSMA-11, highlighting limited bladder uptake by 18F-rhPSMA-7.3.
Figure 3
Figure 3
PSMA PET scan showing evidence for metastatic lymph node disease in a patient with PCa. (A) Ga-68 PMSA-11 PSMA/CT whole body maximum intensity image (MIP) shows a focus of nodular uptake (red arrow) adjacent to the right ureter. (B) Transaxial contrast-enhanced CT demonstrates a 0.3 cm right internal lymph node (red arrow), which was not mentioned on the clinical report. Transaxial slices of the Ga-68 PMSA-11 PSMA/CT show intense PSMA-11 accumulation in the lymph node (red arrow) on fused (C) PET/CT, (D) PET only, and (E) CT only.
Figure 4
Figure 4
A male with PCa with extensive metastatic disease throughout the skeleton and lymph nodes, seen on the pre-radiotheranostics PET and with near complete resolution of disease after radiotheranostic treatments.
Figure 5
Figure 5
CAR-T MOA.
Figure 6
Figure 6
BiTEs MOA.
Figure 7
Figure 7
Antibody–Drug Conjugates MOA.
Figure 8
Figure 8
Summary of the evolving PSMA theranostic landscape, from current clinical use to future approaches.
See this image and copyright information in PMC

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