FOLH1 expression

Total cell-bound activity, rather than added activity, better predicted radiotoxicity in both TP53-wild-type and TP53-null cell lines, indicating that its therapeutic effect is primarily governed by PSMA-mediated uptake rather than p53 status. These results support the therapeutic potential of [212Pb]Pb-AB001 across cells with varying TP53 status and suggest that combining [212Pb]Pb-AB001 with DNA repair or checkpoint inhibitors may enhance treatment efficacy.

[68Ga]Ga-PSMA-11 PET/CT revealed clinically relevant PSMA expression in a subset of mTNBC patients. These results support further investigation of PSMA-targeted RLT in this biomarker-defined population.

By situating PSMA within this broader biomarker landscape, we outline opportunities for theranostic integration, including predictive models, combination therapies and expansion into non-prostate malignancies. Understanding the biology of PSMA in conjunction with novel biomarkers provides a framework for optimising theranostic applications and advancing personalised cancer care.

PSMA tracers are important tools for evaluating intermediate- and high-risk prostate cancer, with limitations in 5-10% of prostate cancers that do not express PSMA. Theranostics are increasingly incorporating PSMA.

This study demonstrated that PSMA is commonly expressed in malignant SGTs, suggesting that PSMA could be effective for targeted imaging and therapeutics in these tumor types.

On the other hand, the synthetic amino acid analog 18F-fluciclovine demonstrated a lesion detection rate of 84% for PSA levels at or above 5, and 62.5% for PSA levels ranging from 0.7 to less than 1. This review concludes with future directions on the paradigm of multi-tracer and dual-targeting strategies, which can effectively address challenges associated with PCa tumor heterogeneity and facilitate personalized approaches in theranostics.

FDG PET/CT restaging showed no recurrence in the nephrectomy bed and a stable FDG-avid right paratracheal mass. After stereotactic body radiation therapy (SBRT) directed to the right paratracheal mass, follow-up PSMA PET/CT showed decreased uptake (SUVmax 4.8), suggesting its usefulness for detecting and monitoring ccRCC.

High tracer accumulation in 70% of the participants suggests a possible use for PSMA-directed radiopharmaceutical therapy in an end-stage setting. However, PSMA expression was not prognostic for outcome, possibly because of the small sample size.

[177Lu]Lu/[225Ac]Ac-PSMA tandem RLT may offer a safe, effective treatment option. Assessment of PSMA expression on pretherapeutic PET predicts response, supporting its use in guiding personalized treatment.

Although PSMA-targeted therapies are primarily used for the management of prostate cancer, they are also being explored in treatment of salivary gland malignancies including adenoid cystic carcinoma. This review explores the mechanisms and clinical manifestations of PSMA-related oral toxicities in the context of prostate cancer, diagnosis, possible mitigation strategies, the need for preclinical models to study regulation of PSMA expression leading to oral toxicities, current challenges and future directions.

Our data highlight the potential utility of ctDNA in optimising patient selection, improving therapeutic monitoring, and dissecting genomic mechanisms of resistance to [177Lu]Lu-PSMA-617, and further prospective validation is warranted.

Single intravenous administration of [99mTc]Tc-DB8, for visualization of GRPR expression in PCa using SPECT imaging was well tolerated in a peptide mass range of 40-120 µg. An injected peptide mass of 80-120 µg/patient and SPECT acquisition 2-4 h pi were found to be optimal for further clinical studies due to the significantly lower activity accumulation in the pancreas and kidneys.