Amino Acid Transport
The transport and metabolism of amino acids is a normal function of all cells. Proliferating cells, such as cancer cells, need to build cellular protein and are likely to have a higher amino acid demand. Regulation of amino acid transporter expression and activity in cancer has also been linked to cancer promoting molecular signalling pathways, such as those mediated by m-tor(1).
Fluciclovine (18F) is transported across cell membranes by amino acid transporters, such as LAT-1 and ASCT2 which are known to be upregulated in many cancers. Oka et al explored the uptake mechanism of fluciclovine (18F) into prostate cancer cell lines in vitro(2) and found that internalisation was mediated predominantly by system ASC transporters (such as ASCT2) or LAT1, depending on availability of Sodium Na+ (Figure1). The same authors also showed in similar experiments that the uptake of fluciclovine (18F) was stimulated by the presence of androgens and could be inhibited by drugs targeting the androgen signalling axis(3).
Figure 1: The Amino Acid Transport mechanisms relevant to fluciclovine (18F)
- Fuchs and Bode; Seminars in Cancer Biology 15 (2005) 254–266
- Oka et al; Nuclear Medicine and Biology 39 (2012) 109–119
- Okudaira et al Mol Imaging Biol (2014) 16:756Y764