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A potent μ-opioid agonist, [C]carfentanil, was prepared by the methylation of carfentanil carboxylic acid with [C]methyl iodide in order to study brain μ-opioid receptors by positron emission tomography. Synthesis (including purification) was completed within 25 min and the radiochemical yield was approximately 40%. The radiochemical purity of the product was more than 99% and its specific activity was 3.7-7.4 GBq/μmol. Biodistribution studies performed in mice after intravenous injection showed a high brain uptake and rapid blood clearance, so a high brain/blood ratio of 1.5-1.8 was found from 5 to 30 min. Regional cerebral distribution studies in the mouse showed a significantly higher uptake of [C]carfentanil by the thalamus and striatum than by the cerebellum, with the radioactivity in the striatum disappearing more rapidly than that in the thalamus. Treatment with naloxone significantly reduced the uptake of [C]carfentanil by the thalamus and striatum. These results indicate that [C]carfentanil binds specifically to brain μ-opioid receptors. [ABSTRACT FROM AUTHOR]

Our previous studies have shown a high accumulation of [I]N,N,N′-trimethyl-N′-(2-hydroxy-3-methyl-5-iodobenzyl)-l,3-propanediamine (HIPDM) in the human pancreas. In this study, the pancreatic accumulation and metabolism of [I]HIPDM were studied in rats to determine the factors influencing its uptake by this organ. In biodistribution studies, [I]HIPDM showed a high uptake by the pancreas similar to that by the brain and lungs, both organs with a low tissue pH. TLC analysis of pancreatic homogenate after the injection of [I]HIPDM showed that it was metabolically stable in this organ. Moreover, in the pancreatic homogenate, the bulk of the radioactivity was recovered from the microsomal fraction, and the radioactivity bound to microsomal particles showed release that was dependent on the Ca or Mg concentration in the incubation medium. These results suggest that the initial pancreatic uptake of [I]HIPDM may be a function of blood flow and governed by the pH gradient hypothesis, while subsequent retention may occur secondary to ionic binding within the pancreas. [ABSTRACT FROM AUTHOR]