[(14)C]Fluciclovine (alias anti-[(14)C]FACBC) uptake and ASCT2 expression in castration-resistant prostate cancer cells.
Nucl Med Biol
; 42(11): 887-92, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26278491
ABSTRACT
INTRODUCTION:
trans-1-Amino-3-[(18)F]fluorocyclobutanecarboxylic acid ([(18)F]fluciclovine, also known as anti-[(18)F]FACBC), is a tracer for positron emission tomography (PET) imaging for detection of tumors such as prostate cancer (PCa). Our previous study showed that ASCT2 (Na(+)-dependent amino acid transporter (AAT)) mediates fluciclovine uptake in androgen-dependent PCa cells; its expression is influenced by androgen, a key hormone in the progression of primary PCa and castration-resistant prostate cancer (CRPC). In this study, we investigated the uptake mechanisms and feasibility of [(18)F]fluciclovine for CRPC in the androgen-dependent PCa cell line LNCaP and LNCaP-derivatives LNCaP-SF and LN-REC4.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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Ácidos Carboxílicos
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Regulação Neoplásica da Expressão Gênica
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Ciclobutanos
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Sistema ASC de Transporte de Aminoácidos
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Neoplasias de Próstata Resistentes à Castração
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article