NUKLEONIKA 2008, 53(4):151-154

 


BIOLOGICAL EVALUATION OF [18F]-NIFEDIPINE AS A NOVEL PET TRACER FOR L-TYPE CALCIUM CHANNEL IMAGING



Hossein Sadeghpour1,2, Amir R. Jalilian2, Mehdi Akhlaghi2, Abbas Shafiee3,
Mohammad Mirzaii2, Ramin Miri3, Fariba Saddadi2

1 Faculty of Pharmacy and Pharmaceutical Sciences Research Center,
Tehran University of Medical Sciences,
P. O. Box 14155-6451, Tehran, Iran
2 Nuclear Medicine Research Group,
Agricultural, Medical and Industrial Research School (AMIRS-NSTRI),
P. O. Box 31585-4395, Karaj, Iran
3 Medicinal & Natural Products Chemistry Research Centre,
Shiraz University of Medicinal Sciences,
P. O. Box 71345-3288, Shiraz, Iran

Due to interesting role of dihydropyridines in cardiovascular diseases and drug resistance studies and lack of a fluorine-18 labeled imaging agent for L-type calcium channel studies, this study was designed. [18F]Dimethyl 2-(fluoromethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 2 was prepared in no-carrier-added (n.c.a.) form from a starting brominated compound in one step at 80°C in Kryptofix2.2.2/[18F]. Compound 2 was administered to normal rats via their tail veins for preliminary biodistribution studies and the ID/g% of the labeled compound was determined up to 3 h post injections. Coincidence images were obtained in rats 5 to 120 min. Radiofluorination on bromo precursor gave a fluorinated compound in 95% radiochemical purity and a 8% yield shown by RTLC and HPLC. Biodistribution studies showed that the tracer is accumulated in the heart in the first few minutes, followed by metabolism resulting in very soluble 18F-containing metabolites eliminated through the urinary tract. In coincidence images, the target organ was shown to be the heart. Lung had high accumulation possibly due to the presence of Ca2+ channels and/or hydrolyzing enzymes showing a significant myocardial uptake at 120 min. The data demonstrates a significant agreement with the reported L-type calcium channels throughout the animal body. To our knowledge, this is the first example of 18F-DHPs in the literature.

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