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. 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). 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.
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. 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). 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.
Authors: J Narula; E R Acio; N Narula; L E Samuels; B Fyfe; D Wood; J M Fitzpatrick; P N Raghunath; J E Tomaszewski; C Kelly; N Steinmetz; A Green; J F Tait; J Leppo; F G Blankenberg; D Jain; H W Strauss Journal: Nat Med Date: 2001-12 Impact factor: 53.440
Authors: H Hara; R M Friedlander; V Gagliardini; C Ayata; K Fink; Z Huang; M Shimizu-Sasamata; J Yuan; M A Moskowitz Journal: Proc Natl Acad Sci U S A Date: 1997-03-04 Impact factor: 11.205
Authors: Heidi Kenis; Hugo van Genderen; Abdel Bennaghmouch; Hilde A Rinia; Peter Frederik; Jagat Narula; Leo Hofstra; Chris P M Reutelingsperger Journal: J Biol Chem Date: 2004-09-20 Impact factor: 5.157
Authors: Jian Gong; Richard Archer; Michael Brown; Seth Fisher; Connie Chang; Matthew Peacock; Christopher Hughes; Bruce Freimark Journal: Mol Imaging Date: 2013-06 Impact factor: 4.488
Authors: Delphine L Chen; Jacquelyn T Engle; Elizabeth A Griffin; J Philip Miller; Wenhua Chu; Dong Zhou; Robert H Mach Journal: Mol Imaging Biol Date: 2015-06 Impact factor: 3.488