RT Journal Article SR Electronic T1 Preparation of 3-[18F]fluoro-2-hydroxypropanoic acid and preliminary tumor PET imaging study JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 608 OP 608 VO 59 IS supplement 1 A1 Wang, Hongliang A1 Dong, Weixuan A1 Ma, Jingxin A1 Wu, Zhifang A1 Li, Sijin YR 2018 UL http://jnm.snmjournals.org/content/59/supplement_1/608.abstract AB 608Objectives: The profiles of tumor containing oxygenated and hypoxic regions is the heterogeneity of tumor, the glycolytic (hypoxic regions) and oxidative (oxygenated regions) tumor cells mutually regulate their access to take up and catabolize lactate is the metabolic symbiotic model of the utilization of lactate for the glucose metabolism of tumor. The in vitro and in vivo studies of the catabolism of exogenous 13C or 14C labeled lactate in breast cancer have confirmed the uptake appeared specific to aerobic tumor regions. And radiolabeled (11C and 14C) lactates were observed the course of oxidative phosphorylation by generation of labeled CO2. However, to our knowledge, noninvasive tumor lactate metabolism imaging has never been performed because of the lack of an adequate radiotracer. In this study, an 18F-fluorine labeled lactate 3-[18F]fluoro-2-hydroxypropanoic acid, 3-[18F] lactate) was synthesized and evaluated as a PET tracer for tumor imaging. Methods: A nucleophilic ring opening reaction was performed for the [18F]-fluorination of the precursor methyl 2-oxiranecarboxylate in tert-amyl alcohol with dried [18F]K222/Cs2CO3/CsF, and the intermediate methyl 3-[18F] fluoro-2-hydroxy-propionate was purified with semi-preparative HPLC. After the dilution of the collected eluent, the intermediate was trapped on two C18 SEP-PAK cartridges, and 2 N NaOH aqueous solution was added into the C18 SEP-PAK cartridges for the hydrolysis. After the hydrolysis, 3-[18F] lactate in the cartridges was drawn through a Alltech IC-H cartridge and a 0.22 μm sterile filter into a sterile vial. ICR mice bearing subcutaneous S180 tumors were administered 3-[18F] lactate intravenously for in vivo PET imaging, and the uptake ratios of tumor to other main tissues were determined from the dissected tissues the after the imaging. Results: The synthesis of 3-[18F] lactate was accomplished in 60 min and with a reproducible radiochemical yield of 15±3% (decay uncorrected) and a high radiochemical purity of more than 95%. PET imaging study showed a significantly high tumor uptake of 3-[18F] lactate was observed in the S180 model mice, and the tumor uptake rate was 5.83±0.29 % ID/g after 60 min postinjection. A significant brain and live uptake was seen without significant bone imaging. The ratios of tumor to blood, muscle, brain and liver was 4.62±0.62, 1.87±0.31, 1.74±0.26 and 1.47±0.21, respectively. Conclusions: The purification of the intermediate methyl 3-[18F] fluoro-2-hydroxy-propionate using HPLC was essential with the presence of a byproduct methyl 2-[18F] fluoro-3-hydroxy-propionate in the nucleophilic ring opening reaction. Although further optimization of preparation and catabolism of 3-[18F] lactate are required, the preliminary in vivo PET imaging results showed the specific tumor uptake of 3-[18F] lactate. And these findings could be used to inform the development of tumor lactate metabolism imaging agents. Acknowledgements: This work was partly supported by the National Natural Science Foundation (No. 81471695 and 81571716), Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (No. 2014134).