Publication costs assisted by Brookhaven National LabcratoryThe reduction of nitro blue tetrazolium (NBT2+) by COf and Of has been studied by the stopped-flow method and the pulse-radiolysis technique. Both reductants form the tetrazolinyl radical, and the rate constants ares-1 and h N B p + + 02-= (5.88 f 0.12) X lo4 M-I s-'. In the absence of other reactants, the tetrazolinyl radicals (NBT',) disappear by a pH-dependent second-order disproportionation reaction to produce monoformazan (MF') and nitro blue tetrazolium (NBT2+) ions. The tetrazolinyl radical (NBT+.) has an absorption maximum at 405 nm with a pH-independent molar extinction coefficient ~4 0 5~~= 15 000 f 350 M-' cm-l. Monoformazan (MF+) has an absorption maximum at 530 nm; its molar extinction coefficient varies from E~~~~~ = 25 400 f 1200 M-' cm-l at pH 9.5-11.0 to €53onm = 12 800 f 640 M-l cm-' at pH 5.7-6.7. Mechanisms for the overall reaction are discussed.
The purpose of this study was to develop a radiopharmaceutical that could be used to selectively image 5-HT1A receptors with positron emission tomography (PET). No-carrier-added 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[18F] fluorobenzamido]ethylpiperazine (p-[18F]-MPPF, 2) was synthesized by the nucleophilic substitution of the corresponding nitro precursor 1 with K[18F]/Kryptofix 2.2.2. in dimethyl sulfoxide (DMSO) at 140 degrees C for 20 min followed by purification with high-performance liquid chromatography (HPLC) in 10% yield in a synthesis time of 90 min from end of bombardment (EOB). Specific activity was 1-4 Ci/microM. Biodistribution studies in rats showed that the initial uptake of 2 in the brain was high (0.7% dose/g tissue at 2 min). It was then rapidly eliminated. Rates of elimination were significantly slower in brain regions with high concentrations of 5-HT1A receptors (hippocampus, cortex, and hypothalamus) than in control regions. The maximum hippocampal/cerebellar ratio was 5.6:1 at 30 min postinjection. Uptake values in serotonergic, but not in control, regions were significantly reduced by prior treatment with either (+/-)-8-OH-DPAT (2 mg/kg, i.v., 5 min prior) or WAY 100635 (1 mg/kg, i.v., 5 min prior). Radioactivity in the femur did not increase with time, suggesting that in vivo defluorination may not be the major route of metabol sm. PET studies of 2 in a monkey demonstrated selective uptake and retention of 2 in the hippocampus. The hippocampal/cerebellar ratio was 3:1 at 30 min postinjection. The ratio was reduced to 1:1 by administering (+/-)-8-OH-DPAT (2 mg/kg, i.v.) 23 min postinjection of 2. Analyses of arterial plasma by HPLC revealed that 20% of radioactivity in the plasma remained as the parent compound 2 at 30 min postinjection. The results suggest that p-[18F]-MPPF may be a useful radioligand for studying cerebral 5-HT1A receptors in humans with PET techniques.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.