CASE REPORT 
Annals of Nuclear Medicine Vol. 12, No. 1, 43-46, 1998 
Absent myocardial accumulation of two different radioiodinated pentadecanoic acids 
Jun HASHIMOTO,* Seiichiro KOSEKI,** Fumio KINOSHITA ** Atsushi KUBO,* Shiro IWANAGA *** Hideo MITAMURA*** and Satoshi OGAWA*** 
*Department of Radiology, and ***Department of Internal Medicine, School of Medicine,Keio University **Department of Internal Medicine, Tokyo Fussa Hospital 
This article presents two cases with preserved myocardial 201Tl uptake and absent uptake of two kinds of radioiodinated fatty acids: iodine-123-labeled 15-(p-iodophenyl)-3-(R.S)-methyl-pentadecanoic acid (BMIPP) and iodine-123-labeled 15-(p-iodophenyl)-9-(R,S)-methyl-pentadecanoic acid (9MPA). Although coronary angiography showed no stenotic lesion and left ventriculography revealed no wall motion abnormality, no myocardial uptake of BMIPP and 9MPA was observed in the first case. In the second case, no myocardial accumulation was recognized even in the initial phase of dynamic SPECT acquired soon after the injection of 9MPA. The results suggest that the non-visualized myocardium was not specific for BMIPP imaging and that rather than the early back diffusion of the tracers from the myocardium, abnormality of the myocardial cell membrane was a possible mechanism accounting for the phenomenon. 
Key words: myocardial SPECT, fatty acid metabolism, I-123-BMIPP, I-123-9MPA 

INTRODUCTION 
NORMAL MYOCARDIUM GENERATES ENERGY for contraction mainly by the oxidation of free fatty acids under the fasting condition, so that radionuclide imaging of the myocardial fatty acid metabolism is expected to be a sensitive indicator of myocardial ischemia. Iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methyl-pentadecanoic acid (BMIPP, Fig. 1) has been used for myocardial imaging, and was designed to be eliminated slowly from the myocardium. Some authors have reported cases without myocardial uptake of BMIPP.1-8 Some of these cases did not show signs of significant coronary stenosis, wall motion abnormality or decreased uptake of 201Tl. We had the opportunity to conduct a clinical trial of another iodinated branched fatty acid, iodine-123-labeled 15-(p-iodophenyl)-9-(R,S)-methyl-pentadecanoic acid (9MPA, Fig. 1), which is washed out faster than BMIPP. In this 
Received September 3, 1997, revision accepted September 3, l997 . For reprint contact: Atsushi Kubo, M.D., Department of Radiology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, JAPAN. 
article, we present two cases with absent myocardial uptake of both of these two iodinated fatty acids. The study was approved by the institutional review board of Keio Univ. Hospital. Written informed consent was obtained from each subject after detailed explanation of the study. No side effects were observed in any of the subjects after administration of BMIPP and 9MPA. 

CASE REPORT 
The first case was a 53-year-old man. He had felt occasional chest pain at rest or during exercise since 1989. Treadmill exercise testing revealed 2 mm asymptomatic ST segment depression. He was admitted to our hospital to undergo coronary angiography in September, 1995. His past history was unremarkable and he did not have any risk factors. In laboratory tests, the counts of blood cells, the levels of serum enzymes, electrolytes, free fatty acids and insulin were within the normal ranges. Mild and transient increase in the blood glucose level was documented (maximum value: 119 mg/dl). Coronary angiography showed no stenotic lesion and left ventriculography revealed no wall motion abnormality. He was referred for imaging with 201Tl, BMIPP and 9MPA in September, 1995. As indicated in Fig. 2, fatty acid scintigrams showed no myocardial uptake of the tracers in spite of intact myocardial accumulation of 201Tl. The second patient was a 64-year-old man with a past history of inferior myocardial infarction in 1994. The counts of blood cells, the levels of serum enzymes, electrolytes and free fatty acids were within the normal ranges. Increased concentrations of blood glucose (136 mg/dl) and insulin (30 /uU/ml) were found in November, 1995. No sign of ischemia was observed in Treadmill testing, and coronary angiography revealed 50% stenosis in the left anterior descending artery and total occlusion in the left circumflex artery. Left ventriculography demonstrated hypokinesis in the posterolateral segment. Thallium-201 scintigraphy performed in 1994 showed a defect in the inferoposterior wall (Fig. 3). No myocardial uptake was observed in BMIPP and 9MPA images obtained in November, 1995 (Fig. 3). Sequential short-axis images obtaed with dynamic SPECT acquisition showed non-visualized myocardium in all frames (Fig. 3). 

DISCUSSION 
Although BMIPP is metabolized in part by alpha- and subsequent beta-oxidation, it is slowly washed out of the myocardium because the methyl-branch inhibits beta-oxidization.9 On the other hand, 9MPA is converted to 3MNA (p-iodophenyl-3-methyl-nanoic acid) after three cycles of beta-oxidation and it is washed out of the myocardium faster. But as it stands, the kinetics of 9MPA have not been reported in detail. Myocardial accumulation of BMIPP was reported to be well correlated with cardiac wall motion and ATP content.3,10,11 Clinically, BMIPP images have been thought to reflect regional myocardial fatty acid metabolism. Many clinical studies reported discrepancies between BMIPP findings and those of 201Tl images in patients with myocardial ischemia, infarction or cardiomyopathy.1,2,12-20 In these articles, most cases presented impaired myocardial fatty acid metabolism with relatively preserved myocardial perfusion. In contrast, there are not so many reports of no myocardial uptake of BMIPP, and the incidence was reported to be 0.3-2.7%.1,2,6-8 It is reported that increased FDG uptake was observed in most of the patients with non-visualized myocardium, suggesting a switch in energy utilization.4,6,7 We could not find any articles mentioning no uptake of other iodinated fatty acids. In the present study, however, both of the two patients had non-visualized myocardium in both BMIPP and 9MPA studies. The results indicated that the phenomenon is not specific to BMIPP imaging. A mild increase in fasting blood glucose was observed in the two patients in our study. Some authors pointed out decreased myocardial uptake of BMIPP in diabetic patients without overt ischemic heart disease19 but abnormality of blood glucose cannot completely explain the non-visualized myocardium, because a lack of uptake was not observed even in patients with advanced diabetes.19 Kurata et al. pointed out that the early myocardial BMIPP uptake correlated positively with plasma insulin levels and negatively with serum free fatty acid levels7 but decreased insulin levels or increased free fatty acid levels were not documented in any patients with the non-visualized myocardium in their studies or ours. Another report suggested underlying hereditary factors in this phenomenon by presenting three cases with no BMIPP uptake in one family.3 Electrocardiography showed QT prolongation in two of the three cases and one patient suffered from non-insulin-dependent diabetes mellitus. Some articles on dynamic BMIPP SPECT acquisition showed that the findings of early images acquired in a few minutes post-injection were well correlated to those of 201Tl images and that discrepancies between BMIPP and 201Tl images were noted in later phases.17,18 These studies concluded that BMIPP was taken up to the myocardium in proportion to myocardial blood flow soon after the administration and that the back diffusion in the later phase resulted in the discrepancies in findings. On the other hand, even in the early phase of the dynamic study with 9MPA, the second patient in our study had a non-visualized myocardium which proved to be viable and well perfused in 201TI imaging. It is also reported that dynamic BMIPP SPECT images revealed no myocardial uptake in any phase.7 These observations suggest that negative myocardial uptake was mainly due to abnormalities of the myocardial cell membrane rather than the early back diffusion of the tracers from the myocardium. It is probable that 9MPA was taken up into myocardial cells not by passive diffusion but by some transportation mechanisms which also contribute to the uptake of BMIPP. Some investigators described carrier-mediated fatty acid transportation of myocardial cells, which is compatible with the results of our study.21.22 In addition, recent reports showed that negative myocardial uptake of BMIPP was observed in seven patients with deficiency of CD36 (type I) which is homologous with the myocardial long-chain fatty acid transporter.5.s,23 Further studies are required to elucidate the relationship between CD36 deficiency and the lack of 9MPA accumulation. 

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