Myocardial fatty acid imaging: Rationale, comparison of ¹¹C- and ¹²³I-labeled fatty acids, and potential clinical utility

Radionuclide imaging of myocardial perfusion and ventricular function are useful for identifying zones of ischemic myocardium. In many cases, additional information can be derived from imaging studies of substrate metabolism. Elegant studies using positron emission tomography (PET) have demonstrated altered glucose and fatty acid metabolism in ischemic tissue. However, the clinical application of PET imaging has been limited to a few centers because of the expense and complexity of the studies. Metabolic imaging would have much greater application if single-photon tracers could be developed that could provide comparable information. Since techniques for the chemical synthesis of radioiodinated fatty acids are relatively straightforward, single-photon imaging of regional fatty acid uptake can be readily performed. Two types of single-photon-labeled fatty acids have been synthesized: (1) straight-chain analogs that undergo near complete catabolism by beta oxidation and (2) branched-chain analogs that cannot be readily catabolized. The initial uptake of both fatty acids is similar, but the branched-chain analogs are retained in the myocardium. Simultaneous recording of regional fatty acid distribution (particularly with ¹²³I-labeled branched-chain analogs) and perfusion (with thallium 201) provides information about the relation of substrate use to perfusion. While this technique has not as yet had widespread clinical testing, the preliminary results are encouraging. In animals with myocardial hypertrophy, zones of well maintained perfusion but decreased fatty acid uptake have been observed; in reperfused myocardium, zones of decreased perfusion relative to fatty acid uptake have been seen; in patients with myocardial ischemia secondary to chronic coronary disease, zones of relative excess fatty acid uptake have also been observed. In this article, we review the current status and potential clinical use of myocardial fatty acid imaging with single-photon radiopharmaceuticals.