This report describes the precursor synthesis and the no-carrier-added (nca) radiosynthesis of the new A(1) adenosine receptor (A(1)AR) antagonist [(18)F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (CPFPX), 3, with fluorine-18 (half-life = 109.6 min). Nucleophilic radiofluorination of the precursor tosylate 8-cyclopentyl-3-(3-tosyloxypropyl)-7-pivaloyloxymethyl-1-propylxanthine, 2, with nca [(18)F]KF under aminopolyether-mediated conditions (Kryptofix 2.2.2/K(2)CO(3)) followed by deprotection was straightforward and, after formulation, gave the radioligand ready for injection with a radiochemical yield of 45 +/- 7%, a radiochemical purity of >98% and a specific radioactivity of >270 GBq/micromol (>7.2 Ci/micromol). Preparation time averaged 55 min. The synthesis proved reliable for high batch yields ( approximately 7.5 GBq) in routine production (n = 120 runs). The radiotracer was pharmacologically evaluated in vitro and in vivo and its pharmacokinetics in rodents determined in detail. After iv injection a high accumulation of radioactivity occurred in several regions of mouse brain including thalamus, striatum, cortex, and cerebellum. Antagonism by the specific A(1)AR antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and N(6)-cyclopentyl-9-methyladenine (N-0840), but not with the A(2)AR antagonist 3,7-dimethyl-1-propargylxanthine (DMPX), indicated specific and reversible binding of the radioligand to A(1)AR in cortical and subcortical regions of interest. In mouse blood at least two polar metabolites formed rapidly (50% at 5 min after tracer application). However, chromatographic analyses of brain homogenate extracts taken 60 min pi showed that >98% of radioactivity was unchanged radioligand. Chromatographic isolation and reinjection of peripherally formed radioactive metabolites revealed no accumulation of radioactivity in mouse brain, probably due to the polarity of the metabolites. These preliminary results suggest that nca [(18)F]CPFPX is a useful radioligand for the noninvasive imaging of the brain A(1)AR.

SUMMARY @A macrocyclic aminopolyether (Kryptofix 2.2.2.) supported labelling method for the preparation of n.c.a. [17-FIfluoroheptadecanoic acid is described. The equimolar complex of potassium carbonate and the aminopolyetheris used to provide nucleophilicity in a homogeneous solution of acetonitrile. Nucleophilic "F-for-Br substitution in the methylester of 17-bromoheptadecanoic acid is accomplished with radiochemical yields of 9 4 + 3%. Subsequent quantitative ester hydrolysis with KOH leads to a simple "one pot" procedure. Minimization of reagent concentrations allows a direct isolation of the product from the reaction mixture by means of reverse phase HPLC. The corrected radiochemical yield of high activity level routine production is 82 + 2% after 90 minutes of synthesis time. The specific activity is > 10,000 Ci/mmol.

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Introduction of fluorine‐18 into various positions of long‐chain fatty acids is described. The potential heart and liver radiopharmaceuticals 16‐18F‐hexadecanoic acid, 17‐18F‐heptadecanoic acid, 2‐18F‐, and (9,10)‐18F‐stearic acid have been prepared by nucleophilic F‐for‐Br exchange in the melt of the corresponding bromofatty acid methylesters in acetamide, followed by alkaline or acid hydrolysis. In the case of 17‐18F‐hepta‐decanoic acid saturation yields of about 30% have been obtained at an optimum reaction temperature of 150 °C and about 1 mg of KF‐carrier.

SUMMARYA complex of the macrocyclic aminopolyether Kryptof ix@ 2.2.2. and potassium carbonate was used to synthesize [ 18F] -CH2BrF from dibromomethane. At the no-carrier-added level the nucleophilic 18F-for-Br exchange gives rise to a corrected radiochemical yield up to 62%.