Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy

摘要

Background Prostate-specific membrane antigen (PSMA) is a promising target for diagnostics and therapy of prostate carcinoma (PCa). Based on the hypothesis that PSMA expression can be modulated by variations in androgen deprivation therapy (ADT), we investigated the binding of a PSMA-directed radiopharmaceutical in vitro in order to get an insight of the interactions between altered premedication and PSMA expression before repetitive PSMA-directed PET/CT for therapy response and targeted therapy implementation. Methods The human castration-resistant PCa cell line VCaP (CRPC) was treated with either 1?nmol/L testosterone (T) over 20 passages yielding the androgen-sensitive cell line (revCRPC) or with 5?μmol/L abiraterone acetate (AA) generating the abiraterone-tolerant subtype CRPC_(AA). In these cell lines, T and AA were varied by either supply or withdrawal of T and AA. PSMA expression of the three cell culture models was detected by Western blot and immunohistochemical staining. For quantitative measurement of tracer uptake, 0.3?nmol/L~(68)Ga-labelled PSMA-HBED-CC peptide (100–300?kBq/ml) was added to different treated parallel cultures ( n ?=?9 each). Time-dependent uptake per 10~(6)cells of each culture was calculated and evaluated. PSMA mRNA expression was investigated by qPCR. Results PSMA expression increased dependently on intensified ADT in all three basic cell lines.~(68)Ga-PSMA-HBED-CC uptake almost doubled during 3?h in all cell lines ( p ?