99mTc-HYNIC-annexin V SPECT imaging of acute stroke and its response to neuroprotective therapy with anti-Fas ligand antibody.
OBJECTIVE
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.


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.


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).


CONCLUSIONS
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.
Blankenberg
Francis G
FG
Division of Pediatric Radiology/Department of Radiology, Stanford University Hospital, 725 Welch Road, Rm #1673, Lucile Packard Children's Hospital, Palo Alto, CA 94305, USA. blankenb@stanford.edu
Kalinyak
Judy
J
Liu
Liping
L
Koike
Maya
M
Cheng
Danye
D
Goris
Michael L
ML
Green
Allan
A
Vanderheyden
Jean-Luc
JL
Tong
David C
DC
Yenari
Midori Anne
MA
D000208:Acute Disease; D000818:Animals; D017304:Annexin A5; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use; D015609:Organotechnetium Compounds; D011379:Prognosis; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020521:Stroke / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D016896:Treatment Outcome
D017304:Annexin A5; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018696:Neuroprotective Agents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C411023:anti-Fas monoclonal antibody; C117287:technetium Tc 99m HYNIC annexin V