Fluorine-18-antimyosin monoclonal antibody fragments: preliminary investigations in a canine myocardial infarct model.
The purpose of this study was to determine in a canine model whether selective myocardial infarct uptake of 18F-labeled antimyosin monoclonal antibody fragments could be achieved in a time frame compatible with the short half-life of this nuclide. Antimyosin monoclonal antibody fragments were labeled with 18F using a succinimidyl [18F]fluorobenzylamine ester acylation agent. Six dogs had myocardial infarction induced by coronary artery occlusion and were reperfused prior to the intravenous administration of 0.6-4.7 mCi of 18F-labeled F(ab')2 (two dogs) or Fab (four dogs). Analysis of tissues obtained 2-4 hr after antibody administration revealed infarct:normal myocardium uptake ratios as high as 14-21:1 for F(ab')2 and 9-12:1 for Fab. Even with Fab, however, prolonged 18F activity in the blood pool interfered with delineation of infarcts by PET imaging. In one dog, perfusion imaging with [13N]ammonia before antimyosin administration was performed, and regions of normal and ischemic myocardium were determined. With these regions of interest, infarct:normal myocardium uptake ratios calculated from the 18F-labeled Fab images increased from 1.5:1 at 1 hr to 4.0:1 at 5 hr. We conclude that 18F-labeled antimyosin fragments may be of value for hot-spot imaging of damaged myocardium with PET; however, blood-pool subtraction techniques will probably be required.
Zalutsky, MR; Garg, PK; Johnson, SH; Utsunomiya, H; Coleman, RE
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