The use of iodinated free fatty acids for assessing fatty acid metabolism

Free fatty acid is a major substrate fuel for normal myocardium. Cardiovascular disease is frequently associated with impairment of fatty acid oxidation. Therefore assessment of fatty acid metabolism may be an important tool for the early detection of myocardial abnormalities and may provide insight into pathologic heart conditions. Although carbon 11-labeled palmitate is a well-established tracer for probing myocardial fatty acid metabolism, a variety of iodinated fatty acid compounds have been introduced for assessing fatty acid metabolism, including straight-chain and branched-chain fatty acid compounds. Straight-chain fatty acid has advantages for measuring fatty acid oxidation on the basis of tracer clearance from the myocardium. Branched-chain fatty acid can be trapped in the myocardium without futher washout and uptake in the myocardium may reflect fatty acid retention and some aspect of fatty acid metabolism. A long tracer retention period makes feasible the acquisition of single-photon emission computed tomographic images. This review examines the characteristics of both types of tracers and our recent clinical experience with β-methyliodophenyl pentadecanoic acid, which has potential for detecting and characterizing both ischemic heart disease and cardiomyopathy.     

Fatty acids for myocardial imaging

Radioiodinated free fatty acids are tracers that can be used to assess both myocardial perfusion and metabolism. There have been several fatty acids and structurally modified fatty acids studied since Evans' initial report of radiolabeled I-123 oleic acid in 1965. The radiolabeling of a phenyl group added to the long chain fatty acids in the omega-terminal position opposite the carboxyl terminal group prevents nonspecific deiodination and the rapid release of free iodine as the tracer undergoes beta-oxidation. The additional inclusion of a methyl or dimethyl group to the chain slows oxidation resulting in prolonged myocardial retention. The longer retention of the radiolabel permits longer image acquisitions more compatible with single photon emission computed tomography (SPECT) imaging, especially with single-detector imaging systems. Several protocols have been implemented using these compounds, particularly 15-(para-iodophenyl)-3-R,S-methyl pentadecanoic BMIPP, to detect abnormal fatty acid metabolism in ischemic heart disease as well as in nonischemic and hypertrophic cardiomyopathies. Successful management of patients with ischemic cardiomyopathies depends on the accurate identification of hibernating myocardium. The studies covered in this review suggest that both IPPA and BMIPP, especially when combined with markers of myocardial perfusion, may be excellent tracers of viable and potentially functional myocardium. Future studies with larger numbers of patients are needed to confirm the results of these studies and to compare their efficacy with that of other available imaging modalities. Cost and distribution issues will have to be resolved for these metabolic tracers to compete in the commercial marketplace. Otherwise they will likely be available only on a limited basis for research use. As progress is made with these issues and with the development of newer imaging systems, the use of radioiodinated and fluorinated fatty acids is likely to be increasingly attractive.     

Cardiac metabolism: A technical spectrum of modalities including positron emission tomography,single-photon emission computed tomography,and magnetic resonance spectroscopy

Noninvasive techniques for the assessment of cardiac metabolism are important for the detection of potentially salvageable tissue in jeopardized areas of the myocardium. The correct identification of hibernating and stunned myocardium in patients with severely depressed cardiac function can have vital therapeutic consequences for the patient. Changes in myocardial fatty acid and glucose metabolism during acute and prolonged ischemia can be traced by positron-emitting or gamma-emitting radiopharmaceuticals. Alternatively,³¹P-labeled magnetic resonance spectroscopy can be used for the assessment of high-energy phosphate metabolism. It is not yet clear which modality will emerge as the most useful in the clinical setting. Positron emission tomography (PET) that uses combinations of flow tracers and metabolic tracers offers unique opportunities for quantification and high-resolution static and rapid dynamic studies. Currently, assessment of glucose metabolism with¹⁸F-fluorodeoxyglucose is regarded as the gold standard for myocardial viability and prediction of improvement of impaired contractile function after revascularization. However, preserved oxidative metabolism may be required for potential functional improvement, and therefore assessment of residual oxidative metabolism by¹¹C-labeled acetate PET may prove to be more accurate than¹⁸F-fluorodeoxyglucose PET, which reflects both anaerobic and oxidative metabolism. Moreover, because fatty acids are metabolized only aerobically, they are excellent candidates for the clinical assessment of myocardial viability and prediction of functional improvement after revascularization. Especially derivatives of fatty acids that are not metabolized but accumulate in the myocyte are attractive for myocardial imaging. Examples are¹²³I-beta-methyl-p-iodophenyl pentadecanoic acid and 15-(o-¹²³I-phenyl)-pentadecanoic acid. These tracers can be detected by planar scintigraphy and single-photon emission computed tomography, which are more economical and widely available than PET. In addition, 511 keV collimators have been developed recently, making the detection of positron emitters by planar scintigraphy and single-photon emission computed tomography feasible. The experience with³¹P-labeled magnetic resonance spectroscopy in humans is still limited. With current magnetic resonance spectroscopic techniques, insufficient spatial resolution is achieved for clinical purposes, but the possibility of serial measurements to monitor rapid changes of phosphate-containing molecules in time makes magnetic resonance spectroscopy very valuable for the research of myocardial metabolism.     

I-123 heptadecanoic acid — value and limitations in comparison with C-11 palmitate

To define the potential of ¹²³I-labeled heptadecanoic acid (IHA) for the noninvasive assessment of myocardial free fatty acid (FFA) metabolism, the kinetics of IHA were compared to those of physiologic ¹¹C-palmitate (CPA). The single-pass myocardial extraction fraction of IHA was lower than that of CPA (0.53±0.11 vs 0.65±0.10 under control conditions). Following an intracoronary injection of IHA and CPA, the myocardial time-activity curves showed biphasic clearance of both tracers. While, for CPA, the half-time of the early phase of the time-activity curve was a function of myocardial oxygen consumption (MVO₂), this phase was not found to reflect the oxidative metabolism of IHA. However, for both tracers, the size of the early phase increased with augmented MVO₂, whereas the size of the late phase decreased. The late phase represents storage of both tracers in triglycerides and phospholipids. Hence, while quantitative measurement of CPA oxidation is possible from the early phase of the time-activity curve, only the ratio between the size of the early and late phase might be of value in assessing myocardial FFA metabolism using IHA.

     

True tracers: comparing FDG with glucose and FLT with thymidine

As PET metabolic imaging becomes routine in clinical practice, there is a tendency to make imaging and data analysis fast and simple, but interpretation of these pictures by visual inspection does not do justice to the power of PET technology. Tissue data and blood data can be analyzed mathematically to provide parametric images of the PET tracer's biochemistry in terms of a transport parameter and a metabolic flux. The methods for parametric imaging with (11)C tracers of glucose and thymidine have been validated, but the short half-life of this radionuclide and the rapid metabolism of these labeled substrates to [(11)C]CO(2) have led investigators to develop (18)F analogs. While (18)F substitution at critical positions in the natural substrate can block metabolism, it has other effects on the transport and metabolism of the analog tracer. The fidelity with which analog tracers mimic tracers of the authentic substrate is critically evaluated for [(18)F]-2-fluoro-2-deoxyglucose and [(18)F]-3'-fluoro-3'-deoxythymidine.     

Effect of impaired fatty acid oxidation on myocardial kinetics of 11C-and 123I-labelled fatty acids

Positron emission tomography with ¹¹C-palmitate and single photon imaging with terminally radioiodinated fatty acid analogues (¹²³I-FFA) were evaluated for the non-invasive assessment of regional myocardial fatty acid metabolism during ischaemia. Decreased uptake of tracer and delayed clearance of activity in the ischaemic myocardium were reported for both ¹¹C-and ¹²³I-labelled compounds. However, since during ischaemia both myocardial blood flow and oxidative metabolism are reduced concomitantly, either factor can be responsible for the changes observed. Experimental preparations in which fatty acid metabolism can be modified independently of flow are helpful for the characterization of the relationship between metabolism and myocardial kinetics of labelled fatty acids. Results obtained during flow-independent inhibition of fatty acid oxidation include the following observations:

• - In dogs with controlled coronary perfusion the rate of clearance of ¹¹ C-palmitate activity is decreased during diminished delivery of oxygen, regardless of whether myocardial perfusion is concomitantly reduced or not.

• - In isolated rabbit hearts perfused at normal flow, the extraction of ¹²³ I-FFA is decreased during hypoxia.

• - During pharmacological inhibition of fatty acid oxidation the deiodination of ¹²³ I_FFA is markedly reduced in rat hearts in vivo and in vitro.

     

Cardiac fatty acid metabolism and ischemic memory imaging with nuclear medicine techniques

There has been a dramatic improvement in the clinical management of myocardial diseases with the advent of cardiac metabolic and molecular imaging. Although both myocardial perfusion and metabolic imaging provide insight of myocardium at risk for infarction or ischemia, it is known that metabolic derangements precede perfusion abnormalities, especially after reperfusion therapy. Deranged myocyte loses its flexibility of choosing the right substrate for energy production and it switches its substrate, especially between fatty acid (FA) and glucose depending on disease condition; for example, predominance of FA metabolism is noted in diabetic heart disease, whereas glucose metabolism is enhanced in pressure overload conditions such as left ventricular hypertrophy. We thus hypothesize that with better technological advancements and different substrates, the metabolic footprint of various heart diseases can be charted out in future to help in the optimization of patient management. This review attempts to discuss the importance of radionuclide-labeled FAs in cardiac metabolic and ischemic memory imaging.     

Radionuclide assessment of myocardial fatty acid metabolism by PET and SPECT

Although fatty acid is a major energy source in the normal myocardium, fatty acid oxidation is easily suppressed in a variety of cardiac disorders. Therefore assessment of fatty acid metabolism may hold an important role for early detection of myocardial abnormalities and provide insights into cardiac pathologic states. C-11 palmitate is a well-established PET tracer to probe myocardial fatty acid metabolism. On the other hand, a variety of iodinated fatty acid compounds have been introduced for assessment of fatty acid metabolism with conventional gamma cameras. These include straight-chain, such as iodopheyl pentadecanoic acid (IPPA), and branch-chain fatty acid compounds, such as beta-methyl iodopheyl pentadecanoic acid (BMIPP). This review article includes the characterization of these tracers and clinical experiences with these tracers for detection and characterizing patients with ischemic heart disease and cardiomyopathy.     

Current status and prospects of new radionuclides and radiopharmaceuticals for cardiovascular nuclear medicine

The rapid emergence of new imaging modalities like positron emission tomography (PET) and single photon emission computerized tomography (SPECT) and their advance into the clinical arena offered new opportunities for, but also stimulated research and development of new radiopharmaceuticals suitable for cardiac imaging. While tracers of myocardial blood flow remained in the center of interest, other trends heralded possibilities of studying more comprehensively cardiac physiology and pathophysiology as, for example, metabolism, the severity of tissue injury, neural activity and membrane function. N-13 ammonia and rubidium-82 became the primary tracers for evaluating and possibly quantifying regional myocardial blood flow with PET, while cationic Tc-99m isonitrile complexes have now reached a stage where high contrast images of the human heart are obtained on planar scintigraphy and SPECT. These radiopharmaceuticals hold considerable promise for routine clinical use. Tracers of metabolism, especially those labeled with positron emitting isotopes as for example, C-11 palmitate, F-18 2-deoxyglucose, are approaching the phase of clinical use and provide information on regional myocardial substrate metabolism and oxidative processes. Less successful and more limited were developments of single photon emitting tracers of metabolism which remained largely confined to radioiodinated fatty acid analogs. Exploration and characterization of the metabolic fate of the radiolabel in tissue and its relation to the externally observed signal have been truly impressive. Tested in humans primarily in western European countries, these tracers promise to yield metabolic information on a more limited scope. Most widely applied are iodohepta- and hexadecanoic acid and, more recently, the aromatic fatty acid analog, paraiodophenylpentadecanoic acid. Labeled monoclonal antibodies rapidly advanced to the point of clinical use. Accurate identification and sizing of acute myocardial infarction is now possible with Tc-99m or indium-111 labeled specific antimyosin antibody fragments. This success stimulated new research activities for use of labeled antibody techniques in other areas as for example, scintigraphic evaluation of formation and presence of vascular thrombi. While promising, these efforts have however remained in an early stage of development. The same holds true for single photon and positron emitting tracers that are suitable for assessing sympathetic neuron densities in myocardium as well as imaging of both cholinergic and adrenergic receptors.(ABSTRACT TRUNCATED AT 400 WORDS)     

正电子核素心肌代谢显像剂的研究进展

心肌细胞利用葡萄糖、脂肪酸、乳酸及酮体等多种底物产生能量,以维持自身的正常舒缩功能。心肌细胞能量代谢的异常改变与多种心脏疾病相关,如心肌缺血和心力衰竭等。放射性核素显像作为一种无创性功能检查方法,能够用于心肌细胞代谢状况的评价。放射性核素心肌代谢显像剂是由放射性核素标记的心肌代谢底物及其类似物,在临床上分为氧代谢显像剂...     

Iodine-123-labelled fatty acids for myocardial single-photon emission tomography: current status and future perspectives

Renewed interest in the clinical use of iodine-123-labelled fatty acids is currently primarily focused on the use of iodine-123-labelled 15-(p-iodophenyl)pentadecanoic acid (IPPA) and modified fatty acid analogues such as 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) which show delayed myocardial clearance, thus permitting single-photon emission tomographic imaging. Interest in the use of BMIPP and similar agents results from the differences which have often been observed in various types of heart disease between regional myocardial uptake patterns of [¹²³I]BMIPP and flow tracer distribution. Although the physiological basis is not completely understood, differences between regional fatty acid and flow tracer distribution may reflect alterations in important parameters of metabolism which can be useful for patient management or therapy planning. These tracers may also represent unique metabolic probes for correlation of energy substrate metabolism with regional myocardial viability. The two agents currently most widely used clinically are¹²³I-labelled IPPA and BMIPP. While [¹²³I]IPPA is commercially available as a radiopharmaceutical in Europe (Cygne) and Canada (Nordion), multicenter trials are in progress in the United States as a prelude to approval for broad use. [¹²³I]BMIPP was recently introduced as Cardiodine for commercial distribution in Japan (Nihon Medi-Physics, Inc.). [¹²³I]BMIPP is also being used in clinical studies on an institutional approval basis at several institutions in Europe and the United States. In this review, the development of a variety of radioiodinated fatty acids is discussed. The results of clinical trials with [¹²³I]IPPA and [¹²³I]BMIPP are discussed in detail, as are the future prospects for fatty acid imaging.     

Cardiac nuclear medicine: positron emission tomography in clinical medicine

Positron-emission tomography (PET) and radioactively labelled substrates permit metabolic studies to be carried out in vivo and in situ with few if any limitations regarding the choice of substrates as long as they can be tagged with positron-emitting radionuclides, especially those like 11C and 13N. With respect to cardiology, 13N-ammonia and 82Rb are helpful in the examination of myocardial perfusion. The evaluation of myocardial glucose and fatty acid metabolism with 18F-deoxyglucose (FDG) and 11C-palmitate has proved to be clinically useful. Thus, myocardial ischemia and hypoxia, infarct size, the transmural extent of the infarction and tissue viability after it can all be examined as can pathological biochemistry in patients with primary or secondary cardiomyopathies. Single-photon-emitting labelled substances such as 123I-labelled fatty acid analogues also provide information equivalent to that which can be gathered by PET for clinical use. Thus, one major task of PET is the validation of methods and the transformation of these methods to single-photon-emitting radiotracers for broad clinical application, in situations where the expense of PET cannot at present be justified.     

Studies of fatty acid metabolism with positron emission tomography in patients with cardiomyopathy

Positron emission tomography (PET) permits in vivo as well as noninvasive study of fatty acid metabolism. Parameters of ¹¹C-palmitate kinetics relate to the oxidation of fatty acids, and palmitic acid uptake is impaired in patients with coronary disease and cardiomyopathy. Normal myocardium shows homogenous fatty acid·metabolism and can resort to alternate substrates. Diseased myocardium exhibits regional heterogeneity in fatty acid uptake and utilization. In patients with cardiomyopathy, distinct patterns of fatty acid metabolism can be observed following changes of substrate availability by application of an oral glucose load. This intervention also enhances the heterogeneity of ¹¹C-palmitic acid (CPA) uptake and clearance. Thus, PET studies with CPA permit the noninvasive demonstration of effects on substrate availability and may help to characterize patients with ventricular dysfunction on the biochemical level.

     

Metabolic positron emission tomography imaging of cancer: Pairing lipid metabolism with glycolysis

The limitations of fluorine-18 fluorodeoxy-D-glucose (FDG) in detecting some cancers has prompted a longstanding search for other positron emission tomography (PET) tracers to complement the imaging of glycolysis in oncology, with much attention paid to lipogenesis based on observations that the production of various lipid and lipid-containing compounds is increased in most cancers. Radiolabeled analogs of choline and acetate have now been used as oncologic PET probes for over a decade, showing convincingly improved detection sensitivity over FDG for certain cancers. However, neither choline nor acetate have been thoroughly validated as lipogenic biomarkers, and while acetyl-CoA produced from acetate is used in de-novo lipogenesis to synthesize fatty acids, acetate is also consumed by various other synthetic and metabolic pathways, with recent experimental observations challenging the assumption that lipogenesis is its predominant role in all cancers. Since tumors detected by acetate PET are also frequently detected by choline PET, imaging of choline metabolism might serve as an alternative albeit indirect marker of lipogenesis, particularly if the fatty acids produced in cancer cells are mainly destined for membrane synthesis through incorporation into phosphatidylcholines. Aerobic glycolysis may or may not coincide with changes in lipid metabolism, resulting in combinatorial metabolic phenotypes that may have different prognostic or therapeutic implications. Consequently, PET imaging using dual metabolic tracers, in addition to being diagnostically superior to imaging with individual tracers, could eventually play a greater role in supporting precision medicine, as efforts to develop small-molecule metabolic pathway inhibitors are coming to fruition. To prepare for this advent, clinical and translational studies of metabolic PET tracers must go beyond simply estimating tracer diagnostic utility, and aim to uncover potential therapeutic avenues associated with these metabolic alterations.     

Myocardial blood flow and glucose uptake after myocardial infarction

Position emission tomography can picture the distribution of flow tracers as well as of metabolic substrates or analogs. Studies of the distribution of these tracers allow to infer information about regional myocardial clearance (flow x extraction) and substrate utilization. In a study of 32 patients after myocardial infarction, we have contrasted flow and substrate utilization to demonstrate ischemic but viable myocardium in the arterial territory of the infarct in a number of patients also specially after fibrinolytic reperfusion. Restoration of blood flow to the ischemic but viable myocardium through coronary bypass or dilatation improves flow from 56.3% to 84.2% of control and restores substrate utilization. In another group of 32 patients studied with the Strontium-82/Rubidium-82 generator, we have demonstrated perfusion changes both in the myocardial infarct area and at a distance. These changes predominate in patients with multiple vessel disease. Combined PET studies of flow and substrate utilization are new tools to study early intervention after myocardial infarction and to document the benefits of revascularization.

     

Cardiac nuclear medicine: Positron emission tomography in clinical medicine

Positron-emission tomography (PET) and radioactively labelled substrates permit metabolic studies to be carried out in vivo and in situ with few if any limitations regarding the choice of substrates as long as they can be tagged with positron-emitting radionuclides, especially those like ¹¹C and ¹³N. With respect to cardiology, ¹³N-ammonia and ⁸²Rb are helpful in the examination of myocardial perfusion. The evaluation of myocardial glucose and fatty acid metabolism with ¹⁸F-deoxyglucose (FDG) and ¹¹C-palmitate has proved to be clinically useful. Thus, myocardial ischemia and hypoxia, infarct size, the transmural extent of the infarction and tissue viability after it can all be examined as can pathological biochemistry in patients with primary or secondary cardiomyopathies. Single-photon-emitting labelled substances such as ¹²³I-labelled fatty acid analogues also provide information equivalent to that which can be gathered by PET for clinical use. Thus, one major task of PET is the validation of methods and the transformation of these methods to single-photon-emitting radiotracers for broad clinical application, in situations where the expense of PET cannot at present be justified.Dedicated to Prof. Heinz Hundeshagen on the occasion of his 60th birthday     

Impaired myocardial accumulation of 15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid in a patient with hypertrophic cardiomyopathy and exercise-induced ischemia due to vasospasm

We encountered a patient with hypertrophic cardiomyopathy complicated with exercise-induced myocardial ischemia. Exercise-stress 99mTc-tetrofosmin imaging demonstrated reversible ischemia in the lateral wall, whereas resting fatty acid imaging with a new beta-methyl branched fatty acid analogue, I-123-15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid (123I-9-MPA), showed impaired uptake and accelerated washout kinetics in the inferoapical and posteroseptal walls but not in the ischemia-related region. These findings suggest that the metabolic derangement is closely related to cardiomyopathy per se rather than exercise-induced myocardial ischemia in this patient with hypertrophic cardiomyopathy and a spastic coronary lesion so that myocardial perfusion and 123I-9-MPA imagings may contribute to clarifying the etiological background of impaired myocardial fatty acid metabolism.     

Ischaemic memory imaging using metabolic radiopharmaceuticals: overview of clinical settings and ongoing investigations

“Ischaemic memory” is defined as a prolonged functional and/or biochemical alteration remaining after a particular episode of severe myocardial ischaemia. The biochemical alteration has been reported as metabolic stunning. Metabolic imaging has been used to detect the footprint left by previous ischaemic episodes evident due to delayed recovery of myocardial metabolism (persistent dominant glucose utilization with suppression of fatty acid oxidation). β-Methyl-p-[¹²³I]iodophenylpentadecanoic acid (BMIPP) is a single-photon emission computed tomography (SPECT) radiotracer widely used for metabolic imaging in clinical settings in Japan. In patients with suspected coronary artery disease but no previous myocardial infarction, BMIPP has shown acceptable diagnostic accuracy. In particular, BMIPP plays an important role in the identification of prior ischaemic insult in patients arriving at emergency departments with acute chest pain syndrome. Recent data also show the usefulness of ¹²³I-BMIPP SPECT for predicting cardiovascular events in patients undergoing haemodialysis. Similarly, SPECT or PET imaging with ¹⁸F-FDG injected during peak exercise or after exercise under fasting conditions shows an increase in FDG uptake in postischaemic areas. This article will overview the roles of ischaemic memory imaging both under established indications and in ongoing investigations.     

15(p-[123I]Iodophenyl)pentadecanoic acid as tracer of lipid metabolism: comparison with [1-14C]palmitic acid in murine tissues

Uptake and turnover of 15-(p-[123I]iodophenyl)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in heart, lung, liver, kidneys, and spleen and compared with that of [1-14C]palmitic acid (PA). High cardiac uptake of both I-PPA (4.4% dose/g) and PA (2.8% dose/g) was followed by a two-component tracer clearance. Kinetics of I-PPA were linked to those of PA in tissues with primary oxidation of free fatty acids or their preferential storage. Tissue lipids of all organs investigated were labeled concordantly by both tracers. Fractional distributions of PA and I-PPA incorporation in tissue lipids were significantly correlated. Thus general pathways of FFA tissue metabolism are traced by this radioiodinated free-fatty-acid analog. High-quality metabolic imaging of the heart is possible by means of I-PPA with conventional scintigraphic equipment or cross-sectional imaging with single photon emission computerized tomography facilities.     

Heterogeneous myocardial distribution of iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in patients with hypertrophic cardiomyopathy.

IT has been proposed that iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (123I-BMIPP) is an agent for myocardial fatty acid metabolism in animal models. The aim of the present study was to determine whether alterations in fatty acid uptake and/or utilization in patients with hypertrophic cardiomyopathy (HCM) could be detected by 123I-BMIPP. Myocardial imaging with 123I-BMIPP and thallium-201 (201Tl) was performed in 14 fasted patients. A dose of 111 MBq of 123I-BMIPP was administered intravenously at rest, and myocardial emission computed tomography was obtained 20 min and 3 h after injection. The 201Tl imaging was also performed within 1 week after the 123I-BMIPP study. The regional myocardial uptake and clearance of 123I-BMIPP and 201Tl were assessed quantitatively. The myocardial distribution of 123I-BMIPP was more heterogeneous than that of 201Tl in patients with HCM. The myocardial uptake of 123I-BMIPP was lower in the anteroseptal region of the left ventricle than in the posterolateral region (74% vs. 85%, P less than 0.001). The anteroseptal wall showed a faster clearance of 123I-BMIPP than the posterolateral wall (33% vs. 27%, P less than 0.01). Both a decreased uptake and rapid clearance of 123I-BMIPP were observed in the hypertrophied myocardium of the anteroseptal wall, where 201Tl uptake was normal or even increased. Myocardial segments with a markedly increased thickness showed a lower uptake and faster clearance of 123I-BMIPP than those with mild hypertrophy (uptake 73% vs. 82%, P less than 0.05; clearance 30% vs. 25%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)