Radionuclide imaging of the synthetic smooth muscle cell phenotype in experimental atherosclerotic lesions.

Although the exact mechanisms of atherogenesis have not yet been elaborated, it is believed to be an inflammatory immunological response of the injured intima. The molecules and cells involved in this inflammatory response may provide specific targets for the development of novel diagnostic modalities. The present review deals with use of antibodies specific for the neoantigens of the vascular smooth muscle cells of the transformed synthetic phenotype for the detection of atherosclerotic lesions, as well as the potential use of the upregulation of the purinoceptors as indicators of the phenotypic transformation of these cells. In addition to the recognition of atherosclerotic lesions, such a strategy may also help identify accelerated proliferating smooth muscle cells associated with postangioplastic restenosis. © 1996, Elsevier Science Inc. (Trends Cardiovasc Med 1996;6:226-232).

Biochemical and bioimaging markers for risk assessment and diagnosis in major cardiovascular diseases: a road to integration of complementary diagnostic tools.

This report from the first International Course on Integrated Biomarkers, Biochemical and Bioimaging Endpoints in Cardiovascular Diagnosis, Prevention, Therapy and Drug Development provides the basis for optimizing diagnostic, prognostic and therapeutic information in four areas of cardiovascular medicine: primary prevention of cardiovascular diseases, acute coronary syndromes, heart failure and stroke. Risk stratification and treatment strategies can be refined and enhanced through integration of bioimaging and biochemical markers to characterize sub-clinical and clinical atherosclerosis. For the integrative approach to be useful, each of the biomarkers must be validated and cost-effective. Clinical decision is the primary level of integration and is based on clinical evaluation and the use of a combination of bioimaging and biochemical markers. The decision to initiate preventive or therapeutic intervention must take into account the factors affecting the levels of expression of the biomarker and the potential input the biomarker has on metabolic processes or modulation of other biomarkers. The optimal approach to intervention must take into consideration the risk-benefit and cost-effectiveness ratios.

Thallium-201: what do we gain from new clinical protocols and acquisition procedures? The Italian Study on Thallium Reinjection/SIRT).

Nine medical centers, equipped with the same gamma camera and computer software, participated in this multicenter study on thallium-201 reinjection imaging. Preliminary findings for the first 143 patients with ischemic heart disease and perfusion defects at stress imaging are reported. Eighty-eight patients were reinjected at rest after conventional stress-redistribution imaging. Another 55 patients were reinjected at rest on a separate day. After segmental comparison of conventional redistribution versus stress imaging, differences > 1 in the segmental scores on a reduced 3 point scale identified 58 patients with irreversible or mainly irreversible defects (dominant scar pattern) and 85 patients with reversible or mainly reversible defects (dominant ischemic pattern). When reinjection was compared to stress images, 24 patients out of 58 with a dominant scar pattern at the conventional analysis were then assigned to the group with a dominant ischemic pattern. No clinical variables or exercise stress data were found to be significantly different in this patient subgroup. Only 4 out of 85 patients with a dominant ischemic pattern were reassigned to a dominant scar pattern after reinjection scoring. These preliminary results of the SIRT study confirm the consistent problem of scar overestimation by conventional stress-redistribution imaging and the clinical value of the thallium-201 reinjection procedure for differentiating viable from necrotic myocardium.

Noninvasive localization of human atherosclerotic lesions with indium 111-labeled monoclonal Z2D3 antibody specific for proliferating smooth muscle cells.

BACKGROUND: Targeting exclusive antigens in atherosclerotic plaques with antibodies may provide a noninvasive means to detect rapidly proliferative atherosclerotic lesions. 111In-labeled negative charge-modified Z2D3 F(ab')2 (Z2D3) specific for an antigen expressed exclusively by proliferating smooth muscle cells has been shown to accumulate in rabbit atherosclerotic plaques. METHODS: The safety, biodistribution, accumulation, and elimination of Z2D3 were assessed in 11 patients who were candidates for carotid endarterectomy. The presence of atheromas in these patients was confirmed by angiography and Doppler ultrasound. Z2D3 (250 microg) labeled with 5 mCi of 111In was administered by slow intravenous injection. Planar and single photon emission computed tomography (SPECT) images were obtained 4, 24, 48, and 72 hours later. Carotid endarterectomy was performed and the surgical specimens were imaged, weighed, gamma-counted, and analyzed by immunostaining. RESULTS: Uptake of Z2D3 at the site of the carotid plaques was observed in the planar and SPECT views at 4 hours in all subjects. In addition, antibody uptake was noted in the contralateral vessel in 5 subjects. SPECT images identified the atherosclerotic plaques with focal uptake. The antibody uptake corresponded with the angiographic location of the disease. Immunohistochemical studies of the endarterectomy specimens confirmed the localization of Z2D3 into the plaque areas containing smooth muscle cells. Adverse drug reactions were not observed. CONCLUSION: This study demonstrates the feasibility of targeting atherosclerotic lesions with negative charge-modified antibody. It also proposes the possibility of selective identification of various components of atherosclerotic plaque, which may contribute to determining strategies of intervention in future.