Conclusions
System ASC, especially ASCT2, could play a major role in [(14)C]fluciclovine uptake into CRPC-like and androgen-dependent PCa cells, suggesting [(18)F]fluciclovine-PET is applicable to the detection of CRPC as well as androgen-dependent PCa. Advance in knowledge: [(18)F]fluciclovine-PET may be applied for the detection of CRPC. Implication for patient care: [(18)F]fluciclovine-PET may permit early intervention for CRPC treatment.
Methods
LNCaP-SF was established after long-term cultivation of LNCaP in steroid-free conditions, and LN-Pre and LN-REC4 were established from LNCaP inoculated in intact and castrated severe combined immunodeficient mice, respectively. Uptake and competitive inhibition experiments were performed with trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid ([(14)C]fluciclovine) to characterize the involvement of AATs in androgen-dependent PCa (LNCaP and LN-Pre) and CRPC-like (LNCaP-SF and LN-REC4) cell lines. AAT expression was analyzed by Western blotting, and [(14)C]fluciclovine uptake in androgen-dependent PCa and CRPC-like cell lines were investigated in the presence or absence of dihydrotestosterone (DHT).
Results
The contribution of Na(+)-dependent AATs to [(14)C]fluciclovine uptake in all cell lines was 88-98%, and [(14)C]fluciclovine uptake was strongly inhibited by L-glutamine and L-serine, the substrates for Na(+)-dependent alanine-serine-cysteine (system ASC) AATs, in the presence of Na(+). DHT enhanced ASCT2 expression in LNCaP, LN-Pre, and LN-REC4, but not in LNCaP-SF, and the responses of ASCT2 expression to DHT correlated with [(14)C]fluciclovine uptake. Conclusions: System ASC, especially ASCT2, could play a major role in [(14)C]fluciclovine uptake into CRPC-like and androgen-dependent PCa cells, suggesting [(18)F]fluciclovine-PET is applicable to the detection of CRPC as well as androgen-dependent PCa. Advance in knowledge: [(18)F]fluciclovine-PET may be applied for the detection of CRPC. Implication for patient care: [(18)F]fluciclovine-PET may permit early intervention for CRPC treatment.