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

Abstract

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.

How Healthy Is the Acutely Reperfused Ischemic Penumbra?

“…A few studies in rodent stroke models have assessed the uptake of 123 I-IMZ by means of ex vivotechniques such as autoradiography and tissue sampling [27,49,50,51,52]. All but one used permanent MCA occlusion (MCAo), and reported expected reductions in 123 I-IMZ uptake in the core [49,50,51,52].…”

“…All but one used permanent MCA occlusion (MCAo), and reported expected reductions in 123 I-IMZ uptake in the core [49,50,51,52]. However, in a small-scale study that used temporary MCAo, 5 days after reperfusion there was a nonsignificant approximately 20% reduction in 123 I-IMZ uptake in cortical areas showing pyknotic neurons but no pass-necrosis [27].…”

Characterization of neuronal damage by iomazenil binding and cerebral blood flow in an ischemic rat model

“…reported using a rat model in which 1-125-iomazenil uptake was linearly correlated with 1-123-IMP uptake in more than 200 regions at I hr after MCA acciusion. 21 Our rats were sacrificed at 1 hr post injection of iomazenil in the same way as those of Al-Tiknti et al The significant reduction in the acute phase and time dependent increase in iomazenil uptake may reflect a sequential CBF increase 2 based on the development of collateral circulation and reperfusion. And an early reduction in iomazenil uptake may be due to an initial irreversible synaptic dismantlement…”

CPD – Education and Self-assessment: Functional imaging in epilepsy

“…The reason for the disappointing results of clinical application of SPECT BZR imaging may be methodological. A single image of iomazenil binding, without any kinetic modelling, may be seriously confounded by changes in regional blood flow [106][107][108][109] . Hence, without performing multiple scans in the same session coupled with measurements of radiotracer in blood, 123 I-iomazenil SPECT may actually be mainly indicating regional blood flow rather than BZR density.…”