Abstract
1031
Objectives: Radioactive iodine-labeled amino acid derivatives such as [123/131I]iodotyrosine are used as cancer theranostic agents due to the increased amino acid transporter expression on cancer cells. However, due to the electron donating group at ortho position, iodine can be easily dissociated from tyrosine. In the present study, we tried to develop 123I-labeled L- and D-iodohistidine that are supposed to be more stable than iodotyrosine. And their uptakes in non-small cell lung cancer (NSCLC) cell lines were studied in vitro and in vivo. Methods: 123I-labeled L- and D-iodohistidine were prepared from L- and D-histidine by iodogen method in pH 7.4 phosphate buffer and were purified by preparative HPLC. Stability test was performed by incubation at 37°C with 0, 0.5 and 5 mM cysteine solution. Cell uptake study of L-[123I]iodohistidine was performed using NSCLC cell lines including H1975, HCC827, and H522. Competitive cell uptake inhibition study was performed using BCH, tryptophan, and serine. SPECT/CT images of HCC827 Xenograft BALB/c nude mice were obtained at 60-100 min after intravenous injection of L- (64 MBq) or D-[123I]iodohistidine (32 MBq). In vivo biodistribution of each radiotracer was evaluated at 10, 60, and 120 min post-injection in normal BALB/c nude mice. Results: Radiolabeling including HPLC purification completed within 30 min, and radiochemical purity was over 98%. Radiochemical yield of the isolated product was 15-20%. L-[123I]iodohistidine was stable in all concentrations of cysteine solution. NSCLC cell lines showed high L-[123I]iodohistidine uptakes: 54% ID/g for H1975, 73% ID/g for HCC827, 28% ID/g for H522 after 45 min incubation. The uptake of L-[123I]iodohistidine was inhibited by BCH, tryptophan, and serine. Especially, the inhibitions by BCH and tryptophan were higher than serine, suggesting the transportation by L-type amino acid transporter (LAT) and by alanine-serine-cysteine (ASC) transporter. However, L-[123I]iodohistidine showed neither high tumor uptake nor high tumor to muscle ratio (1.3) in vivo. On the other hand, D-[123I]iodohistidine showed higher tumor to muscle ratio (3.7) than L-[123I]iodohistidine. Because of rapid excretion from the body, D-[123I]iodohistidine showed lower muscle uptake than L-[123I]iodohistidine. High pancreas uptake and renal tracer clearance were demonstrated for both compounds. Conclusions: 123I-labeled L- and D-iodohistidine were synthesized by a simple iodogen method with a high radiochemical purity. In vitro experiments demonstrated high L-[123I]iodohistidine uptake by NSCLC cells, but in vivo studies confirmed that D-[123I]iodohistidine is a superior tumor imaging agent for SPECT/CT. Acknowledgements: This research was partially supported by NRF-2017M2A2A7A01071134, NRF-2015M2C2A1047687, and HI15C3093.