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To test the affinity of a new F(ab')2 monoclonal antibody (TRF1) against human fragment D dimer of cross-linked fibrin for atherosclerotic plaques free of detectable thrombi, 6 atherosclerotic segments of carotid and femoral artery, and as a control 5 segments of atherosclerosis-free internal mammary artery, were drawn from 11 male patients undergoing bypass surgery. All segments were carefully washed in order to remove possible endoluminal thrombi, and cut to obtain pairs of intimal fragments of similar weight, containing either plaques (n = 16), or fatty streaks (n = 12), or normal endothelium (n = 20). Each fragment underwent a direct binding test to TRF1, or to a non-specific antibody, both labeled with 125I. The activity in each fragment was measured after 3 h of incubation at 37 degrees C, and after washing the fragments every hour for 3 h. TRF1 binding (as percentage of initial activity) was significantly higher (P0.001) in atherosclerotic than in normal fragments (26% +/- 11.5%, vs. 9.2% +/- 3.9% in fatty streaks, and 1.9% +/- 0.6% in normal endothelium), and indirect immunofluorescence confirmed TRF1 uptake within the plaque wall. By contrast, the non-specific antibody did not show any significant binding. These preliminary results demonstrate the high specific affinity of TRF1 for atherosclerotic plaques, probably due to the hemorheologic phenomena that activate platelets and provoke the formation of fragment D dimers of cross-linked fibrin on the plaque surface.

To test the effectiveness of a new F(ab')2 monoclonal antibody against human fragment D-dimer of cross-linked fibrin in the detection of uncomplicated atherosclerotic lesions of the carotid vessel previously documented at echo-color-Doppler and selective arteriographic study, 8 patients underwent a scintigraphic study including dynamic and early and delayed (3 h later) static imaging of the neck after injection of a bolus of 99mTc-labeled monoclonal antibody, and were subsequently operated. Vessel specimens and blood samples were drawn at operation and counted. No adverse reaction occurred after administration of the monoclonal antibody. The atherosclerotic lesion appeared as a focal area of asymmetrical tracer uptake, already visible at early images in four patients, and at delayed images in five. The average tracer uptake ratio between pathological and normal vessels was 1.40+0.24 (P0.05) at time-activity curves derived from dynamic images, 2.17+/-0.97 (P0.05) at early static images and 2.05+/-0.98 (P0.05) at delayed static images, respectively. Mean vessel to blood uptake rate of specimens obtained at operation was 2.22+/-0.59 (P0.001). The study shows that the 99mTc-labeled antibody was found to be safe and capable of detecting atherosclerotic plaques in humans.

The histological characterization of the fibroatheromatous plaques and their histogenesis are still to be defined. Factors responsible for the evolution of intimal components and the mechanisms and stages of fibroatheromatous plaque formation are still largely obscure. Focusing on symptomatic plaques, the aim of this study is to determine whether plaque heterogeneity is the result of a haphazard clustering of various components or an organized pattern in response to risk factors. To this end, 180 carotid plaques from patients affected by transient ischemic attacks (TIA) or by stroke, with angiographic stenosis greater than 50%, were studied after endoarterectomy. Clinical and morphological data were collected by means of a pre-defined protocol, quantified and correlated, by using the discriminant analysis, with age, sex, hypertension, diabetes, hypercholesterolemia and smoking habit. Our results show that the relationships between plaque components are non-random and consistent with the knowledge derived from studies on human and experimental plaques. Moreover, some plaque patterns can be significantly correlated with single risk factors. The fibrous plaque was correlated with aging and diabetes; the granulomatous plaque, rich in giant cells, with the female sex and hypertension; the xanthomatous plaque, rich in foam cells and with extensive alcianophilia, with hypercholesterolemia. In the smokers, finally, the plaques were frequently complicated by mural thrombosis.