Radiolabeled long-chain fatty acids such as 1-(11C)palmitic acid 17-(123I)iodoheptadecanoic acid and 15-(p-(123I)iodophenyl)pentadecanoic acid are used for myocardial imaging. The widespread use of these fatty acids for myocardial imaging presents several distinct limitations which include rapid metabolism and wash-out of the radioactivity from the myocardium. In the case of the radioiodinated fatty acids, high blood levels of radioactivity present an additional problem. The identification of structural features which will increase the myocardial residence time without decreasing the heart uptake of long-chain fatty acids is of interest. Modified fatty acids containing the tellurium heteroatom have been developed by us and show unique prolonged myocardial uptake and low blood levels. Our detailed studies with radioiodinated vinyliodide substituted tellurium fatty acids demonstrated that heart uptake is a function of the tellurium position. Several of these agents are candidates for labeling with iodine-123 and further evaluation. We propose to develop rapid synthetic techniques using organoborane reagents for the introduction of terminal and internal vinyl halogens into long-chain fatty acids containing stable tellurium. The presence of the tellurium heteroatom represents a structural perturbation which results in the prolonged retention of the radiohalogenated fatty acids in the heart tissue. These new synthetic techniques are being used to prepare model iodinated and brominated tellurium fatty acids which are being evaluated in rats. Successful candidates are being tested in a variety of animal species and the results of these extensive biological studies will be used to extrapolate the absorbed radiation dose values to humans to assess the potential clinical usefulness of these new myocardial imaging agents for the evaluation of heart disease. An additional goal is the development of a """"""""kit"""""""" for the rapid synthesis of the most promising candidates for further preclinical testing and potential clinical evaluation in conjunction with medical cooperative investigators.
| Srivastava, P C; Knapp Jr, F F; Callahan, A P et al. (1985) Myocardial imaging agents: synthesis, characterization, and evaluation of (Z)- and (Z,E)-18-[82Br]bromo-5-tellura-17-octadecenoic acids. J Med Chem 28:408-13 |
