Characterisation of [123I]iomazenil Distribution in a Rat Model of Focal Cerebral Ischaemia in Relation to Histopathological Findings

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2003 Oct 10

PMID 14534832

Citations 1

Authors

Tomohito Kaji

Yuji Kuge

Chiaki Yokota

Masafumi Tagaya

Hiroyasu Inoue

Tohru Shiga

Kazuo Minematsu

Nagara Tamaki

Affiliations

Soon will be listed here.

Abstract

Iodine-123 labelled iomazenil ([(123)I]IMZ) has been reported to be a useful marker of neuronal viability. The brain distribution of [(123)I]IMZ, however, has not been correlated with the pathophysiological response in detail after an ischaemic insult. To characterise [(123)I]IMZ as a marker of neuronal viability, we compared its brain distribution with cyclooxygenase-2 (COX-2) expression, DNA fragmentation and cellular integrity. [(123)I]IMZ and [(125)I]IMP were injected into rats with focal cerebral ischaemia for the purpose of dual-tracer autoradiography. COX-2 and microtubule-associated protein-2 (MAP-2, a marker of cellular integrity) were immunostained. In situ DNA polymerase-I-dependent dUTP incorporation into damaged DNA was used as an indicator of DNA fragmentation. Lesion to normal ratios (LNRs) for [(123)I]IMP and [(125)I]IMZ were calculated. [(123)I]IMZ accumulation was preserved in several regions with impaired [(123)I]IMP accumulation. COX-2 expression was occasionally observed, whereas neither DNA fragmentation nor MAP-2 denaturation was detected in these regions. DNA fragmentation and impaired MAP-2 immunostaining were observed only in the regions with reduced LNRs for both tracers. The LNR for [(123)I]IMZ was significantly lower in regions with impaired MAP-2 immunostaining (0.120+/-0.152, P<0.0001), in regions positive for dUTP incorporation (0.488+/-0.166, P<0.0001) and in regions positive for COX-2 expression (0.626+/-0.186, P<0.001) than in histologically normal regions (0.784+/-0.213). Thus, neuronal DNA is still intact and cellular integrity is maintained in the ischaemic regions with preserved [(123)I]IMZ accumulation. The impairment of [(123)I]IMZ accumulation precedes DNA fragmentation and denaturation of cellular integrity. These results provide the molecular basis of [(123)I]IMZ distribution.

Citing Articles

Loss of neuronal integrity: a cause of hypometabolism in patients with traumatic brain injury without MRI abnormality in the chronic stage.

Shiga T, Ikoma K, Katoh C, Isoyama H, Matsuyama T, Kuge Y Eur J Nucl Med Mol Imaging. 2006; 33(7):817-22.

PMID: 16565846 DOI: 10.1007/s00259-005-0033-y.

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