Dual-isotope autoradiographic measurement of regional blood flow and benzodiazepine receptor availability following unilateral middle cerebral artery occlusion.

Single-photon emission tomography (SPET) imaging in patients with complex partial epilepsy has shown that the seizure focus is characterized by both decreased interictal blood flow and decreased uptake of the benzodiazepine (BZ) receptor tracer iodine-123 iomazenil. The purpose of this study was to examine the confounding effect of decreased flow on iomazenil uptake. The left middle cerebral artery of four rats was occluded, and the animals were simultaneously injected with 25 microCi of iodine-125 iomazenil and 500 microCi of the blood flow tracer [123I]iofetamine (N-isopropyl-p-iodoamphetamine). All rats, including two sham, were sacrificed 1 h after injection, a time when uptake of both agents is nearly maximal. Control experiments showed that arterial occlusion for 1 h did not affect the total number of BZ binding sites. Using a dual autoradiographic technique, the uptake of both [123I]iofetamine and [125I]iomazenil was measured in more than 200 regions showing variable levels of reduced flow and expressed as a percentage of the contralateral homotypic area. The straight line fit of % [125I]iomazenil (y axis) versus % [123I]iofetamine (x axis) in all 200 regions had a slope of 0.74. Insofar as the rat is an accurate model of human subjects with epilepsy, these studies suggest that decreased flow to the epileptogenic focus will linearly exacerbate the decrease in uptake secondary to neuropathologic loss of BZ receptors. Thus, for localization of seizure focus, a single SPET image of [123I]iomazenil in an epileptic patient may have greater sensitivity than a comparable blood flow image, because the former is enhanced by both decreased flow and a loss of BZ receptors.