Experimental and clinical experience with iodine 123-labeled iodophenylpentadecanoic acid in cardiology

Iodine 123-labeled iodophenylpentadecanoic acid (IPPA) has been synthesized for investigating myocardial free fatty acid (FFA) metabolism. The diagnostic application of labeled FFA in heart disease may be important, because FFA is the preferred substrate of cardiac energy metabolism at rest in the fasting state. In addition, regional myocardial FFA uptake and regional myocardial blood flow are tightly coupled in normal myocardium with β-oxidation, which is extremely sensitive to oxygen deprivation. This article outlines basic physiologic pathways of cardiac IPPA metabolism in normal, acutely ischemic, and reperfused viable myocardium and summarizes the results of experimental studies in animals, validating the application of IPPA as an¹²³I-labeled fatty acid analog. In addition, the most important clinical studies indicating the clinical use of IPPA for diagnosis of coronary heart disease and myocardial viability are presented.     

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.

     

Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with <Superscript>99m</Superscript>Tc- and <Superscript>123</Superscript>I-labelled probes

Purpose  The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of ¹²³I- and ^99mTc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake. Methods  A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D₂ receptor ligand [¹²³I]IBZM and the cerebral perfusion tracer [^99mTc]HMPAO (1.2–0.4 MBq/g body weight) in healthy mice. The fatty acid [¹²³I]IPPA (0.94 ± 0.05 MBq/g body weight) and the perfusion tracer [^99mTc]sestamibi (3.8 ± 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP₃ receptor. Results  In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [¹²³I]IBZM and of cardiac [^99mTc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [¹²³I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [^99mTc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [¹²³I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight. Conclusion  Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of ¹²³I- and ^99mTc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Relation of myocardial blood flow and initial cardiac uptake of 15-(p-123I-phenyl)-pentadecanoic acid in the canine heart

In 8 pentobarbital-anesthetized mongrel dogs the correlation between regional myocardial blood flow (RMBF) and regional cardiac uptake of 15-(p-123I-phenyl)-pentadecanoic acid (IPPA) was determined. Three animals were studied under control conditions, in three dogs an acute ischemia was produced by LAD ligation, and two dogs were paced at 195 beats/min. RMBF values were 20-50 ml/min X 100 g in acutely ischemic myocardium. 90-120 ml/min X 100 g under normal conditions and 200-250 ml/min X 100 g during pacing-induced stimulation. Total cardiac uptake of IPPA was 4.5-6% of the injected dose. In normal and acutely ischemic myocardium a good correlation between RMBF and IPPA uptake was obtained. Under stimulated conditions only a moderate increase of IPPA accumulation was found. At RMBF values above 150-170 ml/min X 100 g an upper limit of IPPA uptake was observed and can be explained by limited diffusion or an increased utilization of alternative substrates.     

Myocardial scintigraphy with iodine-123 phenylpentadecanoic acid and thallium-201 in patients with coronary artery disease: a comparative dual-isotope study

To characterise the clinical usefulness of serial myocardial scintigraphy with iodine-123 phenylpentadecanoic acid (IPPA) in comparison with thallium-201, dual-isotope investigations were performed in 41 patients with angiographically documented coronary artery disease. Both tracers were administered simultaneously during symptom-limited ergometry. Planar scintigrams were acquired immediately after stress, and delayed imaging was performed after 1 h for IPPA and 4 h for ²⁰¹Tl. Scintigrams were evaluated both qualitatively and quantitatively using a newly developed algorithm for automated image superposition. Initial myocardial uptake of both tracers was closely correlated (r=0.75, p<0.001). Both tracers also revealed a similar sensitivity for the identification of individual coronary artery stenoses 75% (IPPA: 70.0%, ²⁰¹Tl: 66.3%, P=NS) with identical specificity (69.8%). The number of persistent defects, however, was significantly higher with IPPA (P=0.021), suggesting that visual analysis of serial IPPA scintigrams may over-estimate the presence of myocardial scar tissue. On the other hand, previous Q wave myocardial infarction was associated with a decreased regional IPPA clearance (29% ± 11% vs 44%±11% in normal myocardium, P<0.05). The data indicate that serial myocardial scintigraphy with IPPA is essentially as sensitive as scintigraphy with ²⁰¹Tl for the detection of stress-induced perfusion abnormalities. Quantitative analysis of myocardial IPPA kinetics, however, is required for the evaluation of tissue viability.This study was supported by a grant from the Deutsche Forschungsgemeinschaft/Bonn within the SFB 320 Herzfunktion und ihre Regulation, Ruprechts-Karls University, Heidelberg     

Assessment of myocardial viability by dynamic tomographic iodine 123 iodophenylpentadecanoic acid imaging: Comparison with rest-redistribution thallium 201 imaging

Background

This study examined the ability of dynamic ¹²³I-labeled iodophenylpentade-canoic acid (IPPA) imaging to detect myocardial viability in patients with left ventricular (LV) dysfunction caused by coronary artery disease.

Methods and Results

Serial 180-degree single-photon emission computed tomographic (SPECT) images (five sets, 8 minutes each) were obtained starting 4 minutes after injection of 2 to 6 mCi ¹²³I at rest in 21 patients with LV dysfunction (ejection fraction [EF] 34%±11%). The segmental uptake was compared with that of rest-redistribution ²⁰¹Tl images (20 segments/study). The number of perfusion defects (reversible and fixed) was similar by IPPA and thallium (11±5 vs 10±5 segments/patient; difference not significant). There was agreement between IPPA and thallium for presence or absence (κ=0.78±0.03) and nature (reversible, mild fixed, or severe fixed) of perfusion defects (κ=0.54±0.04). However, there were more reversible IPPA defects than reversible thallium defects (7±4 vs 3±4 segments/patient; p=0.001). In 14 patients the EF (by gated pool imaging) improved after coronary revascularization from 33%±11% to 39%±12% (p=0.002). The number of reversible IPPA defects was greater in the seven patients who had improvement in EF than in the patients without such improvement (10±4 vs 5±4 segments/patient; p=0.075).

Conclusions

¹²³I-labeled IPPA SPECT imaging is a promising new technique for assessment of viability. Reversible defects predict recovery of LV dysfunction after coronary revascularization.     

Comparison of 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA) metabolism and kinetics in the isolated rat heart

Time courses of radioactivity (residue curves) were obtained following bolus injection into working rat hearts of two ¹²⁵I-labeled long chain fatty acids: 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA). Residue curves were analyzed in terms of a rapid vascular washout component, an early tissue clearance component, and a very slow late component. For IHDA and IPPA in control hearts, early myocardial clearance kinetics were rate limited by the diffusion of catabolites. Sensitivity of the kinetics to impaired fatty acid oxidation was examination by pretreatment of animals with 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). Decreased fatty acid oxidation was indicated in IHDA and IPPA residue curves by a decrease in the relative size of the early clearance component. Analysis of radiolabeled species in coronary effluent and heart homogenates showed that back diffusion of IPPA was slower than that of IHDA; this discrepancy was most apparent in POCA hearts. In vitro binding assays suggested higher tissue: albumin relative affinity for IPPA than for IHDA. Thus, IPPA early clearance kinetics were more closely related to the clearance of labeled catabolite(s) and were therefore more sensitive to the oxidation rate of long chain fatty acids.     

Similar effect of revascularization on technetium-99msestamibi and 15-(p-iodophenyl)pentadecanoic acid uptake in myocardial infarction patients

To study its usefulness as a tracer for assessment of the perfusion and viability of myocardium, 15-(p-iodophenyl)pentadecanoic acid (IPPA) was compared with technetium-99m sestamibi (MIBI). Dual-tracer single-photon emission tomography rest imaging was performed no more than 2 months before and 3 months after coronary artery bypass grafting in 28 patients with previous anterior (n=13) or inferior (n=15) infarction. The size of MIBI and IPPA defects decreased from 14%±12% and 13%±9% to 10%±11% and 9%±7%, respectively (P<0.001 for both). The MIBI uptake increased in the infarct zones from 35%±11% to 43%±8% (P<0.001), and in the peri-infarct zones from 50%±11% to 55%±10% (P<0.05). The IPPA uptake increased in the infarct zones from 37%±11% to 44%±13% (P<0.001), and in the peri-infarct zones from 51%±11% to 57%±12% (P<0.05). In nine patients with improved regional echocardiographic wall motion score after bypass surgery, the pre-operative uptake values of both MIBI and IPPA in the infarct and peri-infarct zones were on average slightly but not significantly higher than in 19 patients with no observed improvement in regional wall motion score. In patients with improved regional wall motion, the MIBI scans and the IPPA scans showed (non-significant) decreases in defect size and increases in infarct and peri-infarct zone uptake after bypass surgery. Similar (in some cases significant) changes were observed in the patients without improvement in wall motion. Thus IPPA and MIBI provided similar information about perfusion and viability in pre- and postoperative evaluation of patients with clinically evident myocardial infarction and with normal global ejection fraction. Regardless of the tracer used, the resolution capability of the dual-tracer method with a rest imaging protocol was not sufficient to differentiate viable from non-viable infarction defects in unselected individual patients with a normal ejection fraction. Received 5 March and in revised form 5 May 1999     

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.     

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.

     

Similar effect of revascularization on technetium-99m( )sestamibi and 15-(p-iodophenyl)pentadecanoic acid uptake in myocardial infarction patients.

To study its usefulness as a tracer for assessment of the perfusion and viability of myocardium, 15-(p-iodophenyl)pentadecanoic acid (IPPA) was compared with technetium-99m sestamibi (MIBI). Dual-tracer single-photon emission tomography rest imaging was performed no more than 2 months before and 3 months after coronary artery bypass grafting in 28 patients with previous anterior (n=13) or inferior (n=15) infarction. The size of MIBI and IPPA defects decreased from 14%+/-12% and 13%+/-9% to 10%+/-11% and 9%+/-7%, respectively (P<0.001 for both). The MIBI uptake increased in the infarct zones from 35%+/-11% to 43%+/-8% (P<0.001), and in the peri-infarct zones from 50%+/-11% to 55%+/-10% (P<0.05). The IPPA uptake increased in the infarct zones from 37%+/-11% to 44%+/-13% (P<0.001), and in the peri-infarct zones from 51%+/-11% to 57%+/-12% (P<0.05). In nine patients with improved regional echocardiographic wall motion score after bypass surgery, the pre-operative uptake values of both MIBI and IPPA in the infarct and peri-infarct zones were on average slightly but not significantly higher than in 19 patients with no observed improvement in regional wall motion score. In patients with improved regional wall motion, the MIBI scans and the IPPA scans showed (non-significant) decreases in defect size and increases in infarct and peri-infarct zone uptake after bypass surgery. Similar (in some cases significant) changes were observed in the patients without improvement in wall motion. Thus IPPA and MIBI provided similar information about perfusion and viability in pre- and postoperative evaluation of patients with clinically evident myocardial infarction and with normal global ejection fraction. Regardless of the tracer used, the resolution capability of the dual-tracer method with a rest imaging protocol was not sufficient to differentiate viable from non-viable infarction defects in unselected individual patients with a normal ejection fraction.     

Myocardial scintigraphy with iodine-123 phenylpentadecanoic acid and thallium-201 in patients with coronary artery disease: a comparative dual-isotope study.

To characterise the clinical usefulness of serial myocardial scintigraphy with iodine-123 phenylpentadecanoic acid (IPPA) in comparison with thallium-201, dual-isotope investigations were performed in 41 patients with angiographically documented coronary artery disease. Both tracers were administered simultaneously during symptom-limited ergometry. Planar scintigrams were acquired immediately after stress, and delayed imaging was performed after 1 h for IPPA and 4 h for 201Tl. Scintigrams were evaluated both qualitatively and quantitatively using a newly developed algorithm for automated image superposition. Initial myocardial uptake of both tracers was closely correlated (r = 0.75, p < 0.001). Both tracers also revealed a similar sensitivity for the identification of individual coronary artery stenoses > or = 75% (IP-PA: 70.0%, 201Tl: 66.3%, P = NS) with identical specificity (69.8%). The number of persistent defects, however, was significantly higher with IPPA (P = 0.021), suggesting that visual analysis of serial IPPA scintigrams may overestimate the presence of myocardial scar tissue. On the other hand, previous Q wave myocardial infarction was associated with a decreased regional IPPA clearance (29% +/- 11% vs 44% +/- 11% in normal myocardium, P < 0.05). The data indicate that serial myocardial scintigraphy with IPPA is essentially as sensitive as scintigraphy with 201Tl for the detection of stress-induced perfusion abnormalities. Quantitative analysis of myocardial IPPA kinetics, however, is required for the evaluation of tissue viability.     

Prognostic value of iodine-123 labelled BMIPP fatty acid analogue imaging in patients with myocardial infarction

This study was undertaken to evaluate the prognostic value of iodine-123 labelled 15-iodophenyl3-R,S-methyl pentadecanoic acid (BMIPP) imaging in patients with myocardial infarction. BMIPP is an iodinated methyl branched fatty acid analogue which is trapped in the myocardium with little washout, thereby reflecting fatty acid utilization in the myocardium. We previously reported that in patients with myocardial infarction, regions are often observed where reduced BMIPP uptake is seen relative to thallium-201 perfusion at rest. However, the clinical significance of such discordant BMIPP uptake remains unknown. Fifty consecutive patients with chronic myocardial infarction referred for stress thallium scan and coronary arteriography underwent BMIPP imaging at rest. Each patient was in a stable condition at the time of the radionuclide study. Follow-up was performed at a mean interval of 23 months to investigate the prognostic implications of the radionuclide studies. Nine patients had cardiac events during the follow-up period. Univariate analysis showed that the number of discordant BMIPP versus²⁰¹TL uptake segments was the best predictor of future cardiac events (P=0.0245), followed by the presence of discordant BMIPP uptake (P=0.0388) and the number of²⁰¹TL redistribution segments (P=0.0444). When all the clinical and radionuclide variables were analysed by Cox regression analysis, the presence of discordant BMIPP uptake was the best, and an independent, predictor of future cardiac events (²=8.5) followed by the number of coronary stenoses on angiography (²=3.9). These preliminary data suggest that decreased BMIPP uptake relative to²⁰¹TL is a valuable predictor of future cardiac events in patients with myocardial infarction. Areas with such discordant BMIPP uptake may contain jeopardized myocardium where fatty acid utilization has been severely suppressed relative to myocardial perfusion.Presented in part at the 40th Annual Meeting of Society of Nuclear Medicine at Orlando, Florida, June 1994     

The metabolism of 15-p-[123I]-iodophenylpentadecanoic acid in a surgically induced canine model of regional ischemia

The purpose of this study was to examine the longitudinal effect of gradual coronary occlusion on regional myocardial metabolism of 15-p-¹²³I-iodophenyl pentadecanoic acid ([¹²³I]IPPA). Adult dogs were imaged using [¹²³I]IPPA and planar gamma imaging. A thoracotomy was performed and an ameroid constrictor of appropriate size permanently positioned on the left anterior descending coronary artery. The dogs were imaged after injection of 3–5 mCi [¹²³I]IPPA at various times over a 2-week period. With imaging on days 7 and 14, the dogs were paced at a rate of 185. Time-activity curves were generated and t_1/2 values calculated using monoexponential curve fitting. Results indicate a significant increase in t_1/2 between control and 14 days after surgery in the apical wall (29±7 to 53±18 min;P<0.05). Although there was also an increased t_1/2 in the lateral wall, this was not significant (27±8 to 78±99 min;P > 0.05). There was no significant change in t/12 in the septal wall (27±9 to 33±8 min;P>0.05). We conclude that [¹²³I]IPPA is a useful indicator ofThis work was supported by the British Columbia Heart Foundation     

Impairment of regional fatty acid uptake in relation to wall motion and thallium-201 uptake in ischaemic but viable myocardium: Assessment with iodine-123-labelled beta-methyl-branched fatty acid

In coronary artery disease, discrepancy in the uptake of thallium-201 and of methyl-branched fatty acid at rest has been described. The purpose of this study was to evaluate iodine-123 labelled beta-methylbranched fatty acid (BMIPP) myocardial uptake and wall motion at rest in segments with stress-induced ischaemia identified by stress²⁰¹Tl tomography in patients with chronic coronary artery disease.¹²³I-BMIPP myocardial tomography was performed at rest and was compared with the findings of exercise-reinjection²⁰¹Tl tomography in 45 patients with chronic coronary artery disease. Regional wall motion was evaluated by contrast left ventriculography in 36 patients. Among 237 segments with reversible²⁰¹Tl defects, equally decreased uptake on both reinjection²⁰¹Tl and BMIPP images was observed in 93 (39%), more severely decreased uptake of BMIPP in 118 (50%) and more severely decreased uptake of reinjection²⁰¹Tl in 26 (11%). On the other hand, among 90 segments with non-reversible²⁰¹Tl defects, each pattern was observed in 71 (79%), 6 (7%) and 13 (14%) segments, respectively. When comparing the ischaemic segments with and without more severely reduced uptake of BMIPP than of reinjection²⁰¹Tl, wall motion was impaired to a greater extent in the segments with more severely reduced uptake of BMIPP than of reinjection²⁰¹Tl [severe hypo- or dyskinesis was present in 64 (70%) of 91 segments and in 24 (22%) of 110 segments, respectively,P<0.005]. In patients with chronic coronary artery disease, resting fatty acid uptake was frequently more reduced than reinjection²⁰¹Tl in the segments with stress-induced ischaemia, while in most of the fixed perfusion defects BMIPP and reinjection²⁰¹Tl uptake decreased concordantly. In ischaemic myocardium, wall motion was impaired to a greater extent in those segments which showed more severely reduced uptake of BMIPP than of reinjection²⁰¹Tl. In ischaemic but viable myocardium, discordant BMIPP uptake less than reinjection²⁰¹Tl uptake may indicate metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities. In conclusion, the combination of resting BMIPP and stress-reinjection²⁰¹Tl imaging may provide information on metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities.     

Accelerated BMIPP uptake immediately after reperfused ischemia in the isolated rat heart model

Objective  

¹²³I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) can visualize myocardial fatty acid metabolism and has extensive potential for diagnosing cardiac diseases such as acute coronary syndrome in the clinical setting. Increased BMIPP uptake with decreased perfusion occasionally occurs under acute reperfusion ischemia and the kinetics of BMIPP remain unclear. The present study uses the isolated rat heart model to measure kinetic changes in BMIPP under acute reperfusion ischemia.     

Iodophenylpentadecanoic acid-myocardial blood flow relationship during maximal exercise with coronary occlusion

Imaging 123I-labeled iodophenylpentadecanoic acid (IPPA) uptake and clearance from the myocardium following exercise has been advocated as a means of detecting myocardial ischemia because fatty acid deposition is enhanced and clearance prolonged in regions of low flow. However, normal regional myocardial blood flows are markedly heterogeneous, and it is not known how this heterogeneity affects regional metabolism or substrate uptake and thus image interpretation. In five instrumented dogs running at near maximal workload on a treadmill, 131I-labeled IPPA and 15-micron 46Sc microspheres were injected into the left atrium after 30 sec of circumflex coronary artery occlusion. Microsphere and IPPA activity were determined in 250 mapped pieces of myocardium of approximately 400 mg. Myocardial blood flows (from microspheres) ranged from 0.05 to 7.6 ml/min/g. Deposition of IPPA was proportional to regional flows (r = 0.83) with an average retention of 25%. The mean endocardial-epicardial ratio for IPPA (0.90 +/- 0.43) was similar to that for microspheres (0.94 +/- 0.47; p = 0.08). Thus, initial IPPA deposition during treadmill exercise increases in proportion to regional myocardial blood flow over a range of flows from very low to five times normal.     

BMS-747 158-02: A novel PET myocardial perfusion imaging agent

Background BMS-747158-02 is a fluorine 18-labeled pyridaben derivative designed as a new myocardial perfusion imaging agent for use with positron emission tomography (PET). This study evaluated BMS-747158-02 in animal models of cardiac perfusion and compared it with established single photon emission computed tomography agents. Methods and Results In a rat biodistribution study, BMS-747158-02 (15 μCi) had substantially higher myocardial uptake than technetium 99m, sestamibi (100 μCi) at 15 minutes (3.5%±0.3% % ID/g vs 1.9%±0.1% %ID/g) and 120 minutes (3.2%±0.4% of injected dose per gram vs 1.8%±0.0% of injected dose per gram) after intravenous administration. Uptake ratios of heart to lung and liver at 60 minutes were also higher for BMS-747158-02 (12.7±1.4 and 3.7±0.2, respectively) than Tc-99m sestamibi (5.9±0.5 and 2.4±0.4, respectively). In an isolated rabbit heart model at flow rates of 1.66 to 5.06 mL · min⁻¹ · g⁻¹ wet left ventricular weight, the net BMS-747158-02 heart uptake increased proportionally (0.93±0.15 to 2.44±0.40 mL · min⁻¹ · g⁻¹) and to a greater extent than that of thallium 201 (0.76±0.02 to 1.11 ±0.02 mL · min⁻¹ · g⁻¹) or Tc-99m sestamibi (0.49±0.03 to 0.77±0.08 mL · min⁻¹ · g⁻¹). PET imaging with BMS-747158-02 showed a clear and sustained cardiac uptake in rats, rabbits, and nonhuman primates with minimal lung interference and rapid liver clearance. Myocardial perfusion deficit zones created by either permanent left coronary ligation or reperfusion after ligation in rats were both clearly identified on PET cardiac images of BMS-747158-02 and had good agreement with in vitro histology. Conclusions BMS-747158-02 exhibited high and sustained cardiac uptake that was proportional to blood flow, and it represents a new class of PET myocardial perfusion imaging agent.     

Comparison of myocardial fatty acid metabolism with left ventricular function and perfusion in cardiomyopathies: by<Superscript>123</Superscript>I-BMIPP SPECT and<Superscript>99m</Superscript>Tc-tetrofosmin electrocardiographically gated SPECT

Objective: To investigate myocardial fatty acid metabolism and its relationship with left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM).Methods: Thirty-nine patients with cardiomyopathies (58±14 y), comprising 15 DCM and 24 HCM, and 9 age-matched healthy controls were studied with¹²³I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and^99mTc-tetrofosmin (TF) electrocardiographically gated SPECT. As parameters of myocardial fatty acid metabolism, the heart-to-mediastinum ratio (H/M) and global washout of BMIPP were calculated from early and delayed planar images, while regional BMIPP uptake and washout were calculated from SPECT. In TF study, the H/M (H/M-TF) and LV ejection fraction (LVEF) were calculated as global parameters of perfusion and function, while regional TF uptake and wall thickening index were calculated as regional parameters of perfusion and function using the Quantitative Gated SPECT software. The differences in the parameters and the correlations between the parameters from the 2 studies were investigated by one-way ANOVA and multiple linear regression analysis.Results: BMIPP uptake was decreased (p<0.05), and its washout was increased (p<0.05) in DCM and HCM. In multiple linear regression analysis, global BMIPP parameters showed no significant correlation with LVEF (p>0.05), but showed a significant correlation with H/M-TF (p<0.05) in DCM and HCM. According to the partial correlation coefficient, early H/M was the only significant factor (p<0.05) for predicting H/M-TF in DCM and HCM. Multiple linear regression analysis on regional parameters showed regional BMIPP parameters had no correlation with regional function (p>0.05) but had a significant correlation with regional perfusion (p<0.0001) in DCM. In HCM, regional BMIPP parameters showed significant multiple linear correlations with both regional function (p<0.005) and perfusion (p<0.0001). According to the partial correlation coefficients, delayed regional BMIPP uptake was the most significant factor for predicting regional function in HCM, while early regional BMIPP uptake was the only or the most significant factor for predicting regional perfusion in DCM and HCM, respectively.Conclusion: In DCM, BMIPP uptake and washout could not reflect LV function. In HCM, regional delayed BMIPP uptake might be useful for evaluating regional function. In DCM and HCM, early BMIPP uptake might be largely determined by myocardial perfusion.     

Antemortem diagnosis of cardiac sarcoidosis by abnormal uptake of201Tl in bilateral hilar lymph nodes

The antemortem diagnosis of cardiac sarcoidosis is extremely difficult. We present a patient with congestive heart failure and cardiomyopathy of unknown cause who exhibited an abnormal accumulation of²⁰¹Tl in both hilar lymph nodes in addition to a perfusion defect of the left ventricular myocardium. The findings ultimately led to a diagnosis of myocardial sarcoidosis, which was treated successfully with prednisolone. Although such uptake in the hilar nodes has rarely been reported previously, and the mechanism is not known, this was a remarkable finding in diagnosing cardiac sarcoidosis in this case. When the abnormal hilar lymph nodes uptake of²⁰¹T1 is combined with the defect in the left ventricular myocardium, we should take cardiac sarcoidosis into consideration as the cause of secondary cardiomyopathy.