[¹⁴C]Fluciclovine (alias anti-[¹⁴C]FACBC) uptake and ASCT2 expression in castration-resistant prostate cancer cells

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• 作者：Masahiro Ono^a ; ^b ; Shuntaro Oka^b ; ^{shuntaro_oka@nmp.co.jp" class="auth_mail" title="E-mail the corresponding author} ; Hiroyuki Okudaira^b ; Takeo Nakanishi^c ; Atsushi Mizokami^d ; Masato Kobayashi^e ; David M. Schuster^f ; Mark M. Goodman^f ; Yoshifumi Shirakami^b ; ^g ; Keiichi Kawai^a
• 关键词：Fluciclovine ; Anti-FACBC ; ASCT2 ; Prostate cancer ; CRPC ; Positron emission tomography
• 刊名：Nuclear Medicine and Biology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：42
• 期：11
• 页码：887-892
• 全文大小：506 K

文摘

trans-1-Amino-3-[¹⁸F]fluorocyclobutanecarboxylic acid ([¹⁸F]fluciclovine, also known as anti-[¹⁸F]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 [¹⁸F]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[1-¹⁴C]cyclobutanecarboxylic acid ([¹⁴C]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 [¹⁴C]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 [¹⁴C]fluciclovine uptake in all cell lines was 88−98%, and [¹⁴C]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 [¹⁴C]fluciclovine uptake.

Conclusions

System ASC, especially ASCT2, could play a major role in [¹⁴C]fluciclovine uptake into CRPC-like and androgen-dependent PCa cells, suggesting [¹⁸F]fluciclovine-PET is applicable to the detection of CRPC as well as androgen-dependent PCa.

Advance in knowledge

[¹⁸F]fluciclovine-PET may be applied for the detection of CRPC.

Implication for patient care

[¹⁸F]fluciclovine-PET may permit early intervention for CRPC treatment.