Phenylpiperazine-based radiopharmaceuticals for brain imaging. 3. Synthesis and evaluation of radioiodinated 1-alkyl-4-phenylpiperazines.
As part of our program in radiopharmaceutical chemistry we have prepared and evaluated a series of radioiodinated 1-alkyl-4-phenylpiperazines as potential brain-imaging agents. The compounds were chosen on the basis of their synthetic versatility, activation toward electrophilic substitution, and ease of purification. The intermediates 1-6 were readily obtained and converted to the corresponding radioiodinated products 7-12 in 76-91% isolated radiochemical yields. The tissue distribution in rats indicated that the 1-N-butyl derivative 9 possesses the best combination of brain uptake (0.28-0.35% ID X kg/g), retention, and selectivity (brain/blood greater than 20) over the 4-h evaluation period. A subsequent imaging and tissue distribution study in the dog using 131I-labeled 9 supported the results observed in the rat and suggested the potential of this agent as a brain-imaging agent.
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging*; D004285:Dogs; D005260:Female; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D010879:Piperazines