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This finding might be important for the interpretation of 68Ga–PSMA PET images in monitoring therapies with abiraterone and VPC-13566 in prostate cancer patients, but needs to be validated in vivo. Our data indicate that PSA secretion and PSMA expression are differentially regulated upon anti-androgen treatment.
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Both anti-androgens also enhanced 68Ga–PSMA uptake normalized by the number of cells, whereas abiraterone and VPC-13566 reduced 68Ga–PSMA uptake in total LNCaP monolayers treated due to cell death. We found that abiraterone and VPC-13566 upregulate PSMA protein and mRNA expression but block PSA secretion in LNCaP cells. We analyzed modulation of PSMA-mRNA and protein expression, 68Ga–PSMA uptake and regulation of PSA secretion by abiraterone or VPC-13566 in LNCaP cells in vitro.
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To date, it remains unclear how PSMA expression is modulated by anti-hormonal treatment and how it correlates with PSA secretion. PET using PSMA ligands labeled with Fluor-18 or Gallium-68 is the most sensitive and specific imaging modality for detection of metastases in advanced prostate cancer. Therapeutic monitoring of these pharmaceuticals is performed either by measuring PSA levels in serum or by imaging. In recent years, a variety of innovative therapeutics for castration-resistant prostate cancer have been developed, including novel anti-androgenic drugs, such as abiraterone or VPC-13566.