This project seeks to develop the use of radiolabeled low density lipoprotein (LDL) for detecting atherosclerotic plaques (atheromata) in coronary arteries of living patients. The long- range objectives are (i) to monitor noninvasively how plaques grow or regress in individuals as a function of their medical or surgical treatment for atherosclerosis, so as to assess what kinds of treatment are most effective in arresting atherogenesis; and (ii) to better understand the nature of the atheroma-LDL interaction.
Specific aims of the project include (i) to establish biodistribution parameters and radiation absorbed dose estimates for radiolabeled LDL in humans; (ii) to determine which appears the better of two preparations labeled with Tc-99m and I-123, respectively, by observing the localization in the more accessible plaques in the carotids and femorals; (iii) to select the LDL preparation more suitable for detection and localization of atheromata in the coronary arteries; (iv) to develop the techniques and optimize the conditions necessary for effective imaging of radiolabeled LDL associated with coronary artery atheromata; (v) to determine whether some atheromata are detected more easily than others with radiolabled LDL, and, (vi) if so, to establish the structural features of the atheromata the account for this difference. Patients with clinically documented atheromata will be selected for this study. Autologous LDL isolated by ultracentrifugation will be labeled with I-123 or Tc-99m repurified for injection. Distribution of the injected LDL at appropriate intervals will be monitored by gamma camera imaging with gating as necessary. Specific attention will be paid to radioactivity accumulating in the carotid, femoral, and coronary arteries. In each case, the effectiveness of the preparation of radiolabeled LDL for estimating the sizes and locations of atheromata will be validated by another standard method, including detailed histopathologic and biochemical examination of endarterectomy specimens, angiography of coronary artery lesions, or autopsy. Finally, an in vitro assay for the uptake of radiolabeled LDL by endarterectomy specimens will be established.
| Hay, R V; Fleming, R M; Ryan, J W et al. (1991) Nuclear imaging analysis of human low-density lipoprotein biodistribution in rabbits and monkeys. J Nucl Med 32:1239-45 |
