RT Journal Article SR Electronic T1 Photo-catalyzed 18F-fluorination of leucine and leucine analogues for system L imaging JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 65 OP 65 VO 59 IS supplement 1 A1 Matthew Nodwell A1 Hua Yang A1 Milena Colovic A1 Zheliang Yuan A1 Helen Merkens A1 Winnie Fu A1 Rainer Martin A1 Francois Benard A1 Paul Schaffer A1 Robert Britton YR 2018 UL http://jnm.snmjournals.org/content/59/supplement_1/65.abstract AB 65Objectives: Amino acid tracers have been developed as alternatives for FDG-PET because they may provide complementary information to enhanced glycolysis, while improving imaging contrast in certain cancers. Conventional synthesis of 18F-labeled amino acids usually involves multiple-step precursor synthesis, making it difficult to screen a candidate pool and optimise tracer pharmacokinetics. Also, harsh reaction conditions such as heating under basic conditions may temper the intrinsic chirality of the tracers. In response, we have developed an aqueous, ambient temperature photo-fluorination reaction that allows for selective 18F insertion into tertiary C-H bonds of branched and unprotected aliphatic amino acids[1]. We used this method to synthesize and evaluate several leucine analogues as amino acid transporter system L substrates. Methods: [18F]F2 was converted to [18F]NFSI[2], which was then reacted with leucine or leucine analogues in the presence of sodium decatungstate and UV light (Fig.1). The reaction was carried out using either a micro-fluidic chip, or reaction well apparatus. The 18F-fluorinated amino acids were purified by cation exchange column. Their in vitro uptake was evaluated and their biodistribution in healthy or tumor bearing mice were also studied. Results: Several amino acid tracers have been synthesized using this method, including L-[18F]fluoroleucine (FL), L-[18F]fluorohomoleucine (FHL) and L-[18F]fluorobetahomoleucine (FBHL) (decay corrected radiochemical yield ranged from 23.3% to 33.3%). Cell uptake of L-[18F]FL and L-[18F]FHL showed higher uptake in MCF-7 and PC-3 compared to LNCap, consistent with the their LAT1 expression levels. The uptake in PC-3 cells was blocked by system L inhibitor/substrates including BCH, L-Leu and L-Val but not by system A or ACS inhibitor/substrates L-Ser and MeAIB. Healthy animal biodistribution showed high bone uptake for L-FL indicating in vivo defluorination, while L-[18F]FHL and L -[18F]FBL are stable in vivo. L-[18F]FHL biodistribution in PC-3 and U-87 tumor bearing mice at 1h p.i. demonstrated tracer accumulation in both cases (5.9± 0.7%ID/g (n = 4) for U-87, 5.6 ± 3.2%ID/g (n = 5) for PC-3, Fig.1). Conclusion: We have developed a novel method to label unprotected, branched aliphatic amino acid in mild, aqueous conditions. We have used this method to synthesize several system L substrates and L-[18F]FHL stood out as a strong system L tracer. The potential of L-[18F]FHL for tumor imaging was demonstrated in PC-3 and U-87 tumor models. More system L tracers are under investigation using this Methods: References: 1. M. Nodwell, H Yang, M. Čolović, Z. Yuan, H. Merkens, W. Fu, R. E. Martin, F. Bénard, P. Schaffer, R. Britton, J. Am. Chem. Soc., 2017, 139, 3595. 2. H. Teare, E. G. Robins, E. Årstad, S. K. Luthra, V. Gouverneur, Chem. Commun. 2007, 2330.