Radiohalogen-labeled imaging agents. 3. Compounds for measurement of brain blood flow by emission tomography

• Published in: Journal of medicinal chemistry 1984-08, Vol.27 (8), p.1071-1077
• Main Authors: Sargent, Thornton, Shulgin, Alexander T, Mathis, Chester A
• Format: Article
• Language: English
• Subjects: Amphetamines; Animals; Brain - diagnostic imaging; Cerebrovascular Circulation; Dogs; Halogens; Iodine Radioisotopes - administration & dosage; Radionuclide Generators; Regional Blood Flow; Tissue Distribution; Tomography, Emission-Computed; Xenon Radioisotopes
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00374a023

The radioiodine-labeled amines currently available as brain-imaging agents, based on our previous work and that of others, are prepared either by exchange labeling or by direct iodination of a protected intermediate. The intrinsic slowness of these processes limits their potential for use with the positron-emitting 122I, as it has a half-life of only 3.6 min. This isotope has advantages of a low dose to the patient and availability from a generator containing the parent 20-h 122Xe. To develop a radiopharmaceutical in which 122I could be utilized, we prepared a number of secondary and tertiary amines (maintaining the 2,5-dimethoxy substitution pattern which allows direct iodination at the 4-position) with 131I. The organ distributions of these compounds were studied, and the best properties were found in the N,N-dimethyl homologue (2,5-dimethoxy-N,N-dimethyl-4-iodoamphetamine). This compound was successfully synthesized in a matter of seconds, with a chemical yield and radioactive purity both in excess of 90% and an incorporation efficiency of radioiodine of about 40%.