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Defraiteur C, Lemaire C, Luxen A, Plenevaux A: Radiochemical synthesis and tissue distribution of p-[18F] DMPPF, a new 5-HT1A ligand for PET, in rats. Nucl Med Biol. 2006 Jul;33(5):667-75. Epub 2006 Jun 12.
Several studies have demonstrated the potential of p-[(18) F] MPPF as a radiopharmaceutical to study the 5-HT (1A) receptor family in animals and humans. A structural modification leading to a higher radioactive signal at an equipotent dose would greatly enhance this potential. With this goal, the desmethylated 4-(2'-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-fluorobenzamido] ethyl]-pip erazine (p-MPPF), identified as p-DMPPF, was synthesized, labeled with fluorine-18 and evaluated through ex vivo tissue distribution in rats. The new compounds p-DMPPF, p-DMPPNO (2), MEM-p-MPPF and MEM-p-MPPNO (2) were isolated and fully identified ((1) H and (13) C NMR, LC-MS). The final compound, p-[(18) F] DMPPF, was obtained ready for injection, with an overall radiochemical yield of 10% (EOB corrected) within 90 min and a specific activity of 62 GBq/mumol. Tissue distributions showed that the carbon-fluorine bond was stable in vivo and that this compound could cross the blood-brain barrier. For kidney, lung, heart, spleen, bone, testicle, liver and muscle, the percentage of injected dose per gram of tissue obtained with p-[(18) F] DMPPF was of the same order of magnitude as that of p-[(18) F] MPPF. The amount of radioactivity reaching the brain was much higher (approximately fivefold at 60 min) for p-[(18) F] DMPPF compared with p-[(18) F] MPPF, which was taken as reference. The distribution and specificity were in total agreement with the known localization of 5-HT (1A) receptors in rats. The radioactivity increase was more important for specific tissues (hippocampus and frontal cortex) than for cerebellum or striatum, leading to better contrast (hippocampus/cerebellum=5.8 at 60 min). The levels of metabolites found in plasma showed that p-[(18) F] DMPPF appears to be less metabolized than p-[(18) F] MPPF. p-[(18) F] DMPPF deserves further evaluation as a radiopharmaceutical candidate. |
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