Radioiodine-Labeled N,N-Dimethyl-N'-(2-hydroxy-3-alkyl-5-iodobenzyl)-1,3-propanediamines for Brain Perfusion Imaging

Article abstract of DOI:10.1021/jm00356a001

In developing new brain-imaging agents for single photon emission computed tomography (SPECT), we synthesized five radioiodinated N,N-dimethyl-N'-(2-hydroxy-3-alkyl-5-iodobenzyl)-1,3-propanediamines (12-16).The appropriate o-alkylphenol was formylated via a tin(IV) chloride catalyzed reaction.Iodination with iodine monochloride gave the required 3-alkyl-5-iodosalicylaldehyde, which was reductively aminated with 3-(dimethylamino)propylamine and sodium borohydride.The radioactive labeling (>95percent yield) can be achieved by a rapid aqueous exchange reaction in a serum vial at 100 deg C.Biodistribution in rats exhibited high initial brain uptake (0.9 to 1.8percent dose in brain at 2 min), and the brain activity remained about the same at 1 h for all the compounds.The best brain-imaging agent was N,N-dimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine (12), which showed the highest uptake of 1.80 and 2.02percent dose in brain at 2 min and 1 h, respectively.The brain uptake increases when the specific activity of 125I-labeled 12 decreases.An imaging study of <123I>12 in a monkey showed high initial brain uptake as well as high uptake in lungs and liver.The brain uptake persists for at least 1 h.Autoradiography of rat brain sections showed a regional distribution that reflects the cerebral perfusion pattern (high activity in gray matter and low activity in white matter).It is apparent that <123I>12 is readily prepared and is potentially useful for brain perfusion imaging in conjunction with SPECT devices.