Circulation, Vol 85, 298-304, Copyright © 1992 by American Heart Association
MD Cerqueira, JR Stratton, R Vracko, TF Schaible and JL Ritchie
BACKGROUND. The T2G1s monoclonal antifibrin antibody binds specifically to
fibrin but not to fibrinogen. METHODS AND RESULTS. In a canine model of
acute arterial thrombosis, we determined the feasibility of imaging thrombi
using a 99mTc-labeled Fab' fragment. In 14 dogs, 10 carotid and 13 femoral
artery thrombi were produced using 2-hour temporary occlusion, crush
injury, and local thrombin injection methods. A sham- operated carotid
artery served as control. Antifibrin antibody was injected intravenously at
the end of temporary occlusion. Serial planar radionuclide images were
obtained immediately and at 1 and 2 hours. Following killing the dogs at 2
hours, we measured antibody uptake ex vivo in 5-mm-long segments of
thrombus, the adjacent injured artery, and a control artery. Antibody was
cleared from the blood with a mean +/- SD t1/2 of 121 +/- 23 minutes. The
thrombi weighed 218 +/- 140 mg. Antibody uptake in the thrombi was patchy,
and the thrombi were closely adherent to the injured arterial wall. In the
segment with maximal ex vivo antibody uptake, the ratio of control artery
to blood counts/g/sec was 0.65 +/- 0.46, the injured artery-to-blood ratio
was 2.35 +/- 1.01 (p less than 0.0001 versus control), and the
thrombus-to-blood ratio was 4.24 +/- 2.58 (p less than 0.0001 versus
control). In three dogs, an isotype-matched ovarian tumor antibody labeled
with 111In was injected with T2G1s but was not taken up in the thrombus or
the adjacent arterial wall. Visual analysis of the in vivo carotid
radionuclide images showed uptake by 2 hours in all 10 carotid thrombi.
Quantitative image analysis, measured as the thrombus-to-opposite carotid
artery ratio, showed increasing uptake over time with ratios of 1.1 +/-
0.3, 1.6 +/- 2.0, and 2.2 +/- 1.3 on the immediate, 1-hour, and 2-hour
images, respectively. All quantitative ratios of 1.3 or greater were
visually identified. CONCLUSIONS. 99mTc-labeled Fab' fragments of the T2G1s
antibody are taken up specifically by acute arterial thrombi after
intravenous injection. Uptake is progressive over a 2-hour period, and all
thrombi are detected by radionuclide imaging at 2 hours. These results show
that it is feasible to noninvasively detect arterial thrombi within 2 hours
of formation.
ARTICLES
Noninvasive arterial thrombus imaging with 99mTc monoclonal antifibrin antibody
Department of Medicine, University of Washington, Seattle.
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