PMID- 14534832
OWN - NLM
STAT- MEDLINE
DCOM- 20041013
LR  - 20191210
IS  - 1619-7070 (Print)
IS  - 1619-7070 (Linking)
VI  - 31
IP  - 1
DP  - 2004 Jan
TI  - Characterisation of [123I]iomazenil distribution in a rat model of focal cerebral 
      ischaemia in relation to histopathological findings.
PG  - 64-70
AB  - 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.
FAU - Kaji, Tomohito
AU  - Kaji T
AD  - Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, 
      Kita-ku, Sapporo, Japan.
FAU - Kuge, Yuji
AU  - Kuge Y
FAU - Yokota, Chiaki
AU  - Yokota C
FAU - Tagaya, Masafumi
AU  - Tagaya M
FAU - Inoue, Hiroyasu
AU  - Inoue H
FAU - Shiga, Tohru
AU  - Shiga T
FAU - Minematsu, Kazuo
AU  - Minematsu K
FAU - Tamaki, Nagara
AU  - Tamaki N
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20031008
PL  - Germany
TA  - Eur J Nucl Med Mol Imaging
JT  - European journal of nuclear medicine and molecular imaging
JID - 101140988
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Radiopharmaceuticals)
RN  - 40P7XK9392 (Flumazenil)
RN  - 7DVX185FLQ (iomazenil)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/*diagnostic imaging/*metabolism/pathology
MH  - Disease Models, Animal
MH  - Flumazenil/analogs & derivatives/*pharmacokinetics
MH  - Iodine Radioisotopes
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Radionuclide Imaging
MH  - Radiopharmaceuticals/pharmacokinetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tissue Distribution
EDAT- 2003/10/10 05:00
MHDA- 2004/10/14 09:00
CRDT- 2003/10/10 05:00
PHST- 2003/05/14 00:00 [received]
PHST- 2003/07/27 00:00 [accepted]
PHST- 2003/10/10 05:00 [pubmed]
PHST- 2004/10/14 09:00 [medline]
PHST- 2003/10/10 05:00 [entrez]
AID - 10.1007/s00259-003-1319-6 [doi]
PST - ppublish
SO  - Eur J Nucl Med Mol Imaging. 2004 Jan;31(1):64-70. doi: 10.1007/s00259-003-1319-6. 
      Epub 2003 Oct 8.