Iodine-123-labeled phenylpentadecanoic acid (IPPA) has now been commercially available for several years as a tracer to investigate the metabolic status of the myocardium and perfusion in a single investigation. The authors of the paper [1] compared the usefulness of the IPPA fatty acid analogue with that of thallium-201 in one investigation (dual isotope) at maximal, symptomlimited exercise in patients with coronary artery disease (CAD). The main finding of their study was a significantly greater number of persistent defects in the IPPA scans compared to the 2°iT1 scans.We wish to raise several objections to the study protocol, the results, and the conclusions drawn by the authors.Maximal stress would be expected to result in high lactate serum levels, leading to typical metabolic changes in the myocardium which influence IPPA uptake and metabolism:1. The myocardium will shift to lactate as the preferential source of energy production [2].2. Fatty acid oxidation, even in normal perfused myocardial areas, will be prolonged because of the preferential esterification of IPPA into the lipid storage pools [31.3. In this situation uptake will be diminished, especially in ischaemic zones, with increased "backdiffusion" of unmetabolized IPPA highest in ischaemic myocardial regions [4, 5].These factors lead to diminished net uptake, especially in ischaemic zones, which would be expected to result in persistent defects, although these myocardial segments might be viable. Thus, there is no way to meet the demands for these two tracers in a single investigation because maximal stress is required for 2°1T1 studies to decrease flow in regions supplied by stenotic arteries as much as possible, whereas submaximal exercise (or even rest) is required for IPPA studies to maintain the serum lactate level as low as possible, at least if semiquantification of the tracer kinetics is the aim. The authors surprisingly mentioned in the discussion that their results might be influenced by serum levels of competing substrates but did not measure these completely, although routine laboratory methods are available. It is thus our opinion that many of the results and much of thediscussion remain purely speculative, and that the unexpected results might be explained simply by the investigation protocol and thus do not invalidate the clinical usefulness of IPPA scintigraphy.There are some further comments to be made on this paper:1. The authors stated that for a single-photon emission tomography (SPET) study a 20-min rotation time is mandatory and that due to the short myocardial halflife, IPPA SPET is unreliable. These statements are objectively incorrect because the tracer kinetics have been found not to be linear early after administration [5] and we were able to substantiate this experimental finding in patients [7]; consequently sequential IPPA SPET to semiquantitate tracer kinetics is correlated to coronary artery disease with high sensitivity and specificity [8].2. It is not clear what limiting effect the reconstruction algorithm of SPET...
