[en] Introduction: In vitro screening of fluoromethyl bridge-fused ring (BFR) analogues of WAY-100635 (5a, 5b and 5c) has shown a high binding affinity and a good selectivity for the 5-HT_1A receptor. As these compounds were designed to provide PET ligands with high metabolic stability, they are now radiolabeled with fluorine-18 and investigated in vivo. Methods: BFR precursors were synthesized and reacted with fluorine-18 in dry MeCN in the presence of 2,2,2-kryptofix and K₂CO₃. In rats, biodistribution and PET studies were performed using [¹⁸F]5a, [¹⁸F]5b and [¹⁸F]5c. The binding specificity was determined by administration of non-labeled WAY-100635 prior to the radiolabeled ligands. Results: [¹⁸F]5 ligands were synthesized in overall radiochemical yields of 24%–45%, respectively with a radiochemical purity of > 98%. Relatively good hippocampus to cerebellum ratios of 5.55, 4.79 and 5.45, respectively were reached at 45 min pi. However, PET studies indicated defluorination of the radioligands by showing high accumulation of radioactivity in the bones in the order of [¹⁸F]5a ≈ [¹⁸F]5b > [¹⁸F]5c. Conclusion: Also in vivo, the radioligands bind preferentially to the 5-HT_1A receptor. Unfortunately, no metabolic stability with regard to defluorination was observed in rats.

[en] Introduction: 5-[¹⁸F]Fluoro-5-deoxyribose ([¹⁸F]FDR) 3 was prepared as a novel monosaccharide radiotracer in a two-step synthesis using the fluorinase, a C-F bond forming enzyme, and a nucleoside hydrolase. The resulting [¹⁸F]FDR 3 was then explored as a radiotracer for imaging tumours (A431 human epithelial carcinoma) by positron emission tomography in a mice model. Methods: 5-[¹⁸F]Fluoro-5-deoxyribose ([¹⁸F]FDR) 3, was prepared by incubating S-adenosyl-L-methionine (SAM) and [¹⁸F]fluoride with the fluorinase enzyme, and then incubating the product of this reaction, [¹⁸F]-5'-fluoro-5'-deoxadenosine ([¹⁸F]FDA) 2, with an adenosine hydrolase to generate [¹⁸F]FDR 3. The enzymes were freeze-dried and were used on demand by dissolution in buffer solution. The resulting [¹⁸F]FDR 3 was then administered to four mice that had tumours induced from the A431 human epithelial carcinoma cell line. Results: The tumour (A431 human epithelial carcinoma) bearing mice were successfully imaged with [¹⁸F]FDR 3. The radiotracer displayed good tumour imaging resolution. A direct comparison of the uptake and efflux of [¹⁸F]FDR 3 with 2-[¹⁸F]fluoro-2-deoxyglucose ([¹⁸F]FDG) was made, revealing comparative tumour uptake and imaging potential over the first 10–20 min. The study revealed however that [¹⁸F]FDR 3 does not accumulate in the tumour as efficiently as [¹⁸F]FDG over longer time periods. Conclusions: [¹⁸F]FDR 3 can be rapidly synthesised in a two enzyme protocol and used to image tumours in small animal models