Synthesis and radiopharmacology of O-(2-[¹⁸F]fluoroethyl)-L-tyrosine for tumor imaging

The aim of the study was to develop a simple ¹⁸F-labeled amino acid as a PET tracer for cerebral and peripheral tumors. O-(2-[¹⁸F]fluoroethyl)-L- tyrosine (L-[¹⁸F]FET) was synthesized and biologically evaluated. Results of the first human PET study are reported. Methods: No earner added (n.c.a.) and D-[¹⁸F]FET were prepared by ¹⁸F-fluoroethylation of L- and D-tyrosine in a two-step procedure. Biodistribution studies were performed in mice. The metabolic fate of L-[¹⁸F]FET was investigated in plasma, brain, tumor and pancreatic tissue samples using chromatographic procedures. Tumor uptake studies were performed in mammary carcinoma-bearing mice and in mice with the colon carcinoma SW 707. In a human PET study, a 59-y-old man with a recurrent astrocytoma was imaged using n.c.a. L-[¹⁸F]FET. Results: Synthesis of [¹⁸F]FET was accomplished in about 50 min with an overall radiochemical yield of 40%. The uptake of L-[¹⁸F]FET in the brain of mice reached a level >2% ID/g between 30 and 60 min postinjection. The brain uptake of the D- isomer was negligible, indicating blood-brain barrier penetration by a specific amino acid transport system. L-[¹⁸F]FET is not incorporated into proteins. High-performance liquid chromatography (HPLC) analysis of brain, pancreas and tumor homogenates as well as plasma samples of mice at 10, 40 or 60 min postinjection showed only unchanged L-[¹⁸F]FET. Activity uptake in the bone did not exceed 2% ID/g at 40 min postinjection. The brain uptake of L-[¹⁸F]FET in mice bearing mammary carcinomas and colon carcinomas reached 7.1% ± 1.2% ID/g and 6.4% ± 1.7% ID/g 1h postinjection, respectively. In the first human study, L-[¹⁸F]FET-PET allowed a clear delineation of a recurrent astrocytoma. Thirty-five minutes postinjection, the tumor-to- cortex ratio was >2.7. A tumor-to-blood ratio >1.5 was reached at 30 min postinjection and continued to increase. No significant activity accumulation was observed in peripheral organs after approximately 40 min postinjection. Conclusion: The high in vivo stability of L-[¹⁸F]FET, its fast brain and tumor uptake kinetics its low accumulation in nontumor tissue and its ease of synthesis strongly support further evaluation of L-[¹⁸F]FET as an amino acid tracer for cerebral and peripheral tumors.