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99mTc-HYNIC-annexin V SPECT imaging of acute stroke and its response to neuroprotective therapy with anti-Fas ligand antibody.
- Source :
-
European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2006 May; Vol. 33 (5), pp. 566-74. Date of Electronic Publication: 2006 Feb 14. - Publication Year :
- 2006
-
Abstract
- Purpose: The first aim of the study was to determine whether (99m)Tc-HYNIC-annexin V, a marker of cellular stress and apoptosis, can detect ischemic injury in patients with acute stroke. Secondly, we wished to test radiolabeled annexin's ability to monitor therapy in a rodent model of focal ischemic injury.<br />Methods: SPECT imaging of patients was performed between 1 and 2 h after intravenous injection of 30 mCi (1,110 MBq) of tracer. Eight MFL4 (anti-FasL) antibody-treated (400 microg i.p. days 0 and 3) and 21 control adult male Sprague-Dawley rats underwent small animal SPECT imaging with 5-10 mCi (185-370 MBq) of tracer, 1 and 6 days after a 2-h intraluminal thread occlusion of the left middle cerebral artery.<br />Results: Two patients with acute stroke had regions of multifocal annexin uptake that correlated with sites of restricted diffusion on MRI. Anti-FasL antibody treatment significantly reduced annexin uptake by 92% with a 60% decrease in the number of caspase-8 staining (apoptotic) neurons on day 1. On day 6, treated animals had an 80% reduction in tracer uptake with a 75% decrease in infarct size as compared with controls. Annexin uptake in controls and treated animals (day 6) linearly correlated with infarct size (r (2)=0.603, p=0.0036) and the number of TUNEL-positive (apoptotic) nuclei (r (2)=0.728, p=0.00084).<br />Conclusion: Annexin imaging shows foci of increased uptake at sites of ischemic injury in patients with acute stroke. Annexin imaging can assess the effects of therapy for ischemic cerebral injury in rats, suggesting its potential as a non-invasive indicator of drug efficacy in future clinical trials.
- Subjects :
- Acute Disease
Animals
Antibodies, Monoclonal, Murine-Derived
Brain Ischemia etiology
Humans
Male
Neuroprotective Agents therapeutic use
Prognosis
Radiopharmaceuticals
Rats
Rats, Sprague-Dawley
Reproducibility of Results
Sensitivity and Specificity
Stroke complications
Tomography, Emission-Computed, Single-Photon methods
Treatment Outcome
Annexin A5
Antibodies, Monoclonal therapeutic use
Brain Ischemia diagnostic imaging
Brain Ischemia drug therapy
Organotechnetium Compounds
Stroke diagnostic imaging
Stroke drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1619-7070
- Volume :
- 33
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- European journal of nuclear medicine and molecular imaging
- Publication Type :
- Academic Journal
- Accession number :
- 16477433
- Full Text :
- https://doi.org/10.1007/s00259-005-0046-6