✍ Scribed by H.William Strauss
No coin nor oath required. For personal study only.
In this issue of the J o u ~, Narula et al. describe the intriguing concept of direct imaging of atherosclerotic plaque.1 This manuscript is one of many from this productive group, who have developed and tested an array of antibodies for imaging cardiovascular diseases, including antimyosin for acute myocardial necrosis 2 and antifibrin for the detection of pulmonary emboli? The antibody for detecting atherosclerosis, Z2D3, is particularly interesting because it targets proliferating smooth muscle cells, a key component of the atheromatous lesion. The authors explore the important factor of antibody affinity on lesion visualization by comparing the ability of two antibodies, with a 10-fold difference in affinity, raised against the same smooth muscle antigen, to visualize lesions in the aorta of rabbits injured both physically by balloon de-endothelialization and chemically by feeding the animals a hyperlipidemic diet. The investigators found a nearly fourfold increase in localization with the higher affinity antibody, which confirms the importance of antibody affinity on lesion localization. Visualization of lesions, however, even with the high-affinity antibody, was marginal.
It is likely that the success of imaging atherosclerosis in the rabbit with an injured aorta will be difficult to replicate in other species. Although the high-affinity antibody achieves a lesion/normal aorta ratio of 5.89, it only achieves a lesion to blood ratio of 1.05. This observation suggests that this exciting approach to direct visualization of plaque will have to be followed by many enhancements before a clinically useful technology will emerge.
To provide reliable diagnostic images, at least 0.5% of the injected radiopharmaceutical should be delivered per gram of lesion (in comparison with the 0.112% dose per gram in the present investigation). Major sources of background activity, such as blood and normal vessels, will have to contain near zero concentration to permit visualization of small lesions (target to background ratios will have to be >10:1 to visualize lesions of 1 to 2 ram). It is unlikely that an antibody or a conventional Fab fragment can perform in this fashion. An Fv fragment or one of the smaller molecular recognition units may have these characteristics. Alternatively, a peptide or small molecule could be considered because they
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