Radiopharmacology and PET of O-3-(2-[18F]fluoroethyl)-L-DOPA ([18F]OFED) - a new fluorine-18 labeled phenylalanine derivative

1163 Objectives The newly developed [18F]fluoroethylated DOPA [18F]OFED has similar structural characteristics like the typical L-type amino acid transporter (LAT) radiotracers 6-[18F]fluoro-L-dihydroxy phenylalanine ([18F]FDOPA), 3-methoxy-6-[18F]fluoro-L-dihydroxy phenylalanine ([18F]OMFD), and O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), which are routinely used in PET cancer diagnostics. Therefore, we analyzed the radiopharmacological, toxicological and dosimetric parameters of [18F]OFED in peripheral preclinical tumor models to evaluate the potential of [18F]OFED in diagnostic PET. Methods The radiosynthesis of [18F]OFED is based on a nucleophilic aliphatic substitution with [18F]fluoride. The cell uptake (HT-29, FaDu, PC3, THP-1), biodistribution, metabolism and kinetics were studied in rats and HT-29 tumor bearing mice. For toxicological evaluation 9.12 mg OFED/kg body weight were injected and the rats were observed over 48 days. Results The [18F]OFED was produced in high radiochemical yield (47%), radiochemical purity of 95-98% and the specific activity of 45-81 GBq/µmol. The [18F]OFED cell uptake in vitro was blocked by serine, MeAIB, sodium azide, and BCH, temperature dependent, and the largest transport was observed in FaDu, followed by HT29, PC3, THP-1 cells. In mice 1 h after injection the highest [18F]OFED uptake (SUV) was found in the pancreas (1.3±0.4), kidneys (0.7±0.1), femur (0.5±0.3), and tumors (0.4±0.3). The uptake in the brain reached 0.14±0.04. The tumor-to-blood and -to-muscle ratios were 3.4 and 1.5, respectively. [18F]OFED was not further metabolized, only after the kidney passage in the urine one metabolite was found. No evidence for any toxicological effects was observed. Significant radiation doses were calculated for the bladder wall, kidneys, and pancreas. Conclusions The [18F]OFED accumulation in tumor and normal tissues was preferentially carried out by sodium independent LAT. The biodistribution and kinetics show the typical behavior of the DOPA derived radiotracers. The absorbed radiation dose in the body depends on the activity retention in the bladder. The negligible metabolism permits to use the image-derived input and response functions in the PET studies without metabolite correction. The easy GMP like radiosynthesis, the high radiochemical yield and specific activity, and the high active LAT driven tumor uptake provide a great potential of the [18F]OFED for amino acid transporter based quantitative PET diagnostics in peripheral tumors.