Evaluation of [123I]Isopropyliodoamphetamine as a Tracer for Local Cerebral Blood Flow Using Direct Autoradiographic Comparison

Abstract

We investigated [123I]isopropyliodoamphetamine (IMP) for potential use in the autoradiographic determination of local cerebral blood flow (LCBF) in animals. The technique of direct autoradiographic comparison, derived from double radionuclide autoradiography, was used to compare the simultaneous uptakes of IMP and [14C]iodoantipyrine (IAP), a reference tracer, in awake and anesthetized rats. This new technique offers several advantages over the previously developed methods of comparing tracers, brain uptake index and first pass extraction ratio. These include the avoidance of disrupting normal cerebral blood–brain tracer exchange and the ability to compare uptakes at substructural levels, whereas the other methods are limited to larger areas. Mean values of LCBF obtained with IMP agreed closely with those using IAP, from 20 to 300 ml/100 g/min. Because IMP was found to have an extremely high effective brain:blood partition coefficient, approximately 25:1, a linear uptake tracer model could be used for IMP yielding more precise values than could IAP for LCBF values above 150. IMP was found to measure choroid plexus flows much more accurately than IAP, values being greater than 500 for IMP compared to approximately 200 for IAP. Because the mechanism of the extremely high partition coefficient of IMP is not yet defined, however, care must be used in measuring LCBF with IMP where the trapping mechanisms of normal vessels may be disrupted.