Synthesis and characterization of fluorinated and iodinated pyrrolopyrimidines as PET/SPECT ligands for the CRF1 receptor

Fluorine-18 labeled fluorobutyl[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-p yrrolo [2,3-d] pyrimidin-4-yl]ethylamine (FBPPA) and iodine-123 labeled but yl[2,5-dimethyl-7-(4-iodo-2,6-dimethylphenyl)-7H-pyrrolo[2, 3-d] pyrimidin- 4-yl]ethyl-amine (IBPPA) were synthesized in the development of a CRF recep tor ligand. The methods of synthesis, in vitro binding assays, radiolabelin g and in vivo tissue distribution in rats are described. Fluorine-18 labele d FBPPA was prepared with high specific activity (3 x 10(4) Ci/mmol) by nuc leophilic displacement with an average radiochemical yield of 6% (EOB). Iod ine-123 labeled IBPPA was prepared by electrophilic iododestannylation with good yield (60%) and high specific activity (3.3 x 10(3) Ci/mmol). The ret ention of FBPPA and IBPPA in the pituitary was good (1.16% i.d./g and 2.35% i.d./g respectively at 60 min). However, the accumulation of radioactivity in the brain for both radiotracers was very low at all time points of the study, which demonstrated the difficulties for these radiopharmaceuticals t o penetrate the blood brain barrier (BBB). (C) 2001 Elsevier Science Inc. A ll rights reserved.