Abstract
In metastatic castration-resistant prostate cancer (mCRPC), low prostate-specific membrane antigen (PSMA) avidity constrains the efficacy of 177Lu-PSMA radioligand therapy (RLT). Preclinical studies suggest that valproate may upregulate PSMA expression. We report a 58-year-old man with mCRPC exhibiting disease progression despite multimodal therapy, including chemotherapy, 177Lu-PSMA RLT, and immuno-therapy. He was considered for RLT rechallenge; however, pre-treatment 99mTc-PSMA scintigraphy demonstrated only mild avidity in metastatic lesions, rendering therapy inadvisable. He was subsequently administered sodium valproate for 2 weeks, but repeat scintigraphy revealed diminished PSMA uptake and target-to-background ratios in metastatic lesions. This case suggests a possible association between sodium valproate administration and reduced PSMA tracer uptake, underscoring the need for additional clinical observations to validate these findings.