Prognosis and recurrence in cardiac sarcoidosis: Serial assessment of BMIPP SPECT and FDG-PET.

BACKGROUND: We analyzed 18F-Fludeoxyglucose positron emission tomography (FDG-PET) and 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) performed for cardiac sarcoidosis (CS) patients taking prednisolone, identified recurrence by FDG-PET, and investigated BMIPP as a recurrence and prognostic factor in CS. METHODS AND RESULTS: CS patients who underwent BMIPP and FDG-PET within 2 months were enrolled. The recurrence-free group included patients with standardized uptake value (SUVmax) < 4 in the myocardium consecutively for ≥ 2 years. The total BMIPP SPECT defect score (BDS) was used to estimate myocardial damage. The predictability of the initial BDS and SUVmax for major adverse cardiac events (MACE) was analyzed using Kaplan-Meier analysis. Overall, 73 patients and 250 BMIPP and FDG-PET sets were analyzed retrospectively (mean follow-up, 3.5 years). The BDS was significantly greater for the recurrence group (N = 21) vs recurrence-free group (20 ± 13 vs 14 ± 12, P = 0.041). Patients with BDS ≥16 had a significantly higher MACE rate than patients with BDS < 16 (log-rank test, P = 0.016). However, MACE occurrence was comparable between patients with SUVmax ≥ 4 and < 4. CONCLUSIONS: BDS is a predictive marker of recurrence and MACE. SUV is not related to MACE. Recurrence, defined by prednisolone treatment-induced SUV variability, was observed in approximately 30% of CS patients.

Preclinical Pharmacokinetics and Dosimetry Studies of 124I/131I-CLR1404 for Treatment of Pediatric Solid Tumors in Murine Xenograft Models.

Cancer is the second leading cause of death for children between the ages of 5 and 14 y. For children diagnosed with metastatic or recurrent solid tumors, for which the utility of external-beam radiotherapy is limited, the prognosis is particularly poor. The availability of tumor-targeting radiopharmaceuticals for molecular radiotherapy (MRT) has demonstrated improved outcomes in these patient populations, but options are nonexistent or limited for most pediatric solid tumors. 18-(p-iodophenyl)octadecylphosphocholine (CLR1404) is a novel antitumor alkyl phospholipid ether analog that broadly targets cancer cells. In this study, we evaluated the in vivo pharmacokinetics of 124I-CLR1404 (CLR 124) and estimated theranostic dosimetry for 131I-CLR1404 (CLR 131) MRT in murine xenograft models of the pediatric solid tumors neuroblastoma, rhabdomyosarcoma, and Ewing sarcoma. Methods: Tumor-bearing mice were imaged with small-animal PET/CT to evaluate the whole-body distribution of CLR 124 and, correcting for differences in radioactive decay, predict that of CLR 131. Image volumes representing CLR 131 provided input for Geant4 Monte Carlo simulations to calculate subject-specific tumor dosimetry for CLR 131 MRT. Pharmacokinetics for CLR 131 were extrapolated to adult and pediatric humans to estimate normal-tissue dosimetry. In neuroblastoma, a direct comparison of CLR 124 with 124I-metaiodobenzylguanidine (124I-MIBG) in an MIBG-avid model was performed. Results: In vivo pharmacokinetics of CLR 124 showed selective uptake and prolonged retention across all pediatric solid tumor models investigated. Subject-specific tumor dosimetry for CLR 131 MRT presents a correlative relationship with tumor-growth delay after CLR 131 MRT. Peak uptake of CLR 124 was, on average, 22% higher than that of 124I-MIBG in an MIBG-avid neuroblastoma model. Conclusion: CLR1404 is a suitable theranostic scaffold for dosimetry and therapy with potentially broad applicability in pediatric oncology. Given the ongoing clinical trials for CLR 131 in adults, these data support the development of pediatric clinical trials and provide detailed dosimetry that may lead to improved MRT treatment planning.

Impact of PET and MRI threshold-based tumor volume segmentation on patient-specific targeted radionuclide therapy dosimetry using CLR1404.

Variations in tumor volume segmentation methods in targeted radionuclide therapy (TRT) may lead to dosimetric uncertainties. This work investigates the impact of PET and MRI threshold-based tumor segmentation on TRT dosimetry in patients with primary and metastatic brain tumors. In this study, PET/CT images of five brain cancer patients were acquired at 6, 24, and 48 h post-injection of 124I-CLR1404. The tumor volume was segmented using two standardized uptake value (SUV) threshold levels, two tumor-to-background ratio (TBR) threshold levels, and a T1 Gadolinium-enhanced MRI threshold. The dice similarity coefficient (DSC), jaccard similarity coefficient (JSC), and overlap volume (OV) metrics were calculated to compare differences in the MRI and PET contours. The therapeutic 131I-CLR1404 voxel-level dose distribution was calculated from the 124I-CLR1404 activity distribution using RAPID, a Geant4 Monte Carlo internal dosimetry platform. The TBR, SUV, and MRI tumor volumes ranged from 2.3-63.9 cc, 0.1-34.7 cc, and 0.4-11.8 cc, respectively. The average ± standard deviation (range) was 0.19 ± 0.13 (0.01-0.51), 0.30 ± 0.17 (0.03-0.67), and 0.75 ± 0.29 (0.05-1.00) for the JSC, DSC, and OV, respectively. The DSC and JSC values were small and the OV values were large for both the MRI-SUV and MRI-TBR combinations because the regions of PET uptake were generally larger than the MRI enhancement. Notable differences in the tumor dose volume histograms were observed for each patient. The mean (standard deviation) 131I-CLR1404 tumor doses ranged from 0.28-1.75 Gy GBq-1 (0.07-0.37 Gy GBq-1). The ratio of maximum-to-minimum mean doses for each patient ranged from 1.4-2.0. The tumor volume and the interpretation of the tumor dose is highly sensitive to the imaging modality, PET enhancement metric, and threshold level used for tumor volume segmentation. The large variations in tumor doses clearly demonstrate the need for standard protocols for multimodality tumor segmentation in TRT dosimetry.

Contrast-enhanced CT using a cationic contrast agent enables non-destructive assessment of the biochemical and biomechanical properties of mouse tibial plateau cartilage.

Mouse models of osteoarthritis (OA) are commonly used to study the disease's pathogenesis and efficacy of potential treatments. However, measuring the biochemical and mechanical properties of articular cartilage in these models currently requires destructive and time-consuming histology and mechanical testing. Therefore, we examined the feasibility of using contrast-enhanced CT (CECT) to rapidly and non-destructively image and assess the glycosaminoglycan (GAG) content. Using three ex vivo C57BL/6 mouse tibial plateaus, we determined the time required for the cationic contrast agent CA4+ to equilibrate in the cartilage. The whole-joint coefficient of friction (µ) of 10 mouse knees (some digested with Chondroitenase ABC to introduce variation in GAG) was evaluated using a modified Stanton pendulum. For both the medial and lateral tibial plateau cartilage of these knees, linear regression was used to compare the equilibrium CECT attenuations to µ, as well as each side's indentation equilibrium modulus (E) and Safranin-O determined GAG content. CA4+ equilibrated in the cartilage in 30.9 ± 0.95 min (mean ± SD, tau value of 6.17 ± 0.19 min). The mean medial and lateral CECT attenuation was correlated with µ (R(2) = 0.69, p < 0.05), and the individual medial and lateral CECT attenuations correlated with their respective GAG contents (R(2) ≥ 0.63, p < 0.05) and E (R(2) ≥ 0.63, p < 0.05). In conclusion, CECT using CA4+ is a simple, non-destructive technique for three-dimensional imaging of ex vivo mouse cartilage, and significant correlations between CECT attenuation and GAG, E, and µ are observed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1130-1138, 2016.

Therapeutic combination of radiolabeled CLR1404 with external beam radiation in head and neck cancer model systems.

BACKGROUND AND PURPOSE: CLR1404 is a phospholipid ether that exhibits selective uptake and retention in malignant tissues. Radiolabeled CLR1404 enables tumor-specific positron-emission tomography (PET) imaging ((124)I) and targeted delivery of ionizing radiation ((131)I). Here we describe the first preclinical studies of this diapeutic molecule in head and neck cancer (HNC) models. MATERIAL AND METHODS: Tumor-selective distribution of (124)I-CLR1404 and therapeutic efficacy of (131)I-CLR1404 were tested in HNC cell lines and patient-derived xenograft tumor models. Monte Carlo dose calculations and (124)I-CLR1404 PET/CT imaging were used to examine (131)I-CLR1404 dosimetry in preclinical HNC tumor models. RESULTS: HNC tumor xenograft studies including patient-derived xenografts demonstrate tumor-selective uptake and retention of (124)I-CLR1404 resulting in a model of highly conformal dose distribution for (131)I-CLR1404. We observe dose-dependent response to (131)I-CLR1404 with respect to HNC tumor xenograft growth inhibition and this effect is maintained together with external beam radiation. CONCLUSIONS: We confirm the utility of CLR1404 for tumor imaging and treatment of HNC. This promising agent warrants further investigation in a developing phase I trial combining (131)I-CLR1404 with reduced-dose external beam radiation in patients with loco-regionally recurrent HNC.

Assessment of myocardial metabolic disorder associated with mediastinal radiotherapy for esophageal cancer -a pilot study.

BACKGROUND: To evaluate the dose-effect relations for myocardial metabolic disorders after mediastinal radiotherapy (RT) by performing iodine-123 ß-methyl-iodophenyl pentadecanoic acid (I-123 BMIPP) scintigraphy. METHODS: Between 2011 and 2012, we performed I-123 BMIPP scintigraphy for patients with esophageal cancer before and six months after curative mediastinal RT. Single photon emission computed tomography (SPECT) images of pre-RT and post-RT were registered into RT dose distributions. The myocardium was contoured, and the regional RT dose was calculated. Normalization is required to compare pre- and post-RT SPECT images because the uptake pattern is changed due to the breathing level. Normalization was applied on the mean of SPECT counts in regions of the myocardium receiving less than 5 Gy. Relative values in each dose region (interval of 5 Gy) were calculated on the basis of this normalization for each patient. The reduction in the percent of relative values was calculated. RESULTS: Five patients were enrolled in this study. None of the patients had a past history of cardiac disease. The left ventricle was partially involved in RT fields in all patients. The patients received RT with median total doses of 60-66 Gy for the primary tumor and metastatic lymph nodes. Concomitant chemotherapy consisting of cisplatin or nedaplatin and 5-fluorouracil with RT was performed in 4 patients. All patients had reduced uptake corresponding to RT fields. Dose-effect relations for reduced uptake tended to be observed at 6 months after RT with mean decreases of 8.96% in regions at 10-15 Gy, 12.6% in regions at 20-25 Gy, 15.6% in regions at 30-35 Gy, 19.0% in regions at 40-45 Gy and 16.0% in regions at 50-55 Gy. CONCLUSIONS: Dose-effect relations for myocardial metabolic disorders tended to be observed. We may need to make an effort to reduce high-dose mediastinal RT to the myocardium in RT planning.

Simultaneous dual-isotope imaging based on an artificial neural network for evaluating myocardial perfusion and fatty acid metabolism.

BACKGROUND: We contrived a scatter correction method based on an artificial neural network (ANN) and applied it to the simultaneous evaluation of myocardial perfusion and fatty acid metabolism in single-photon emission computed tomography (SPECT). METHODS: The count data of three energy windows were used as inputs of the ANN. The count ratios of the estimated primary-to-total photons for (99m)Tc and (123)I, which were used to reconstruct (99m)Tc and (123)I images, were calculated using the ANN. In a phantom study, single- and dual-isotope imaging with (99m)Tc/(123)I and (201)Tl/(123)I was performed by means of a cardiac phantom simulating patients with and without obesity. In a human study, five normal volunteers and ten patients with myocardial infarction underwent myocardial perfusion and fatty acid metabolism imaging with single and dual SPECT with combinations of (99m)Tc-methoxyisobutylisonitrile/(123)I-beta-methyl(p-iodophenyl)pentadecanoic acid (BMIPP) and (201)Tl/(123)I-BMIPP as tracers. RESULTS: Technetium-99m yielded more homogeneous images than (201)Tl because of the lower degree of photon attenuation, especially in the condition of obese patients, resulting in clearer visualization of the perfusion-metabolism mismatch. Dual (99m)Tc/(123)I SPECT offered comparable images with single SPECT in assessing myocardial damage. CONCLUSIONS: The method effectively separated (99m)Tc and (123)I primary photons and proved applicable to (99m)Tc/(123)I dual-isotope myocardial SPECT.

The possible role of nuclear imaging in assessment of the cardiac resynchronization therapy effectiveness in patients with moderate heart failure.

BACKGROUND: The aim of the study was to elucidate the role of nuclear medicine imaging in the selection of candidates for cardiac resynchronization therapy (CRT) and in the evaluation of CRT effectiveness METHODS: We studied 28 patients (19 male and 9 female) with dilated cardiomyopathy (DCM) and heart failure (HF). Before implantation of CRT device, all patients underwent SPECT with (99m)Tc-MIBI at rest to evaluate the myocardial perfusion, (123)I-BMIPP to evaluate the myocardial metabolism, and gated cardiac blood-pool SPECT (GBPS) to assess the myocardial contractile function. Following CRT, all patients were examined with 99mTc-MIBI SPECT and GBPS 12 ± 3 months after the intervention. RESULTS: All patients after CRT were divided into three groups. The first group included 10 patients with LVEF increased by more than 10 % (hyperresponders), the 2nd group included 11 patients with an increase in EF of more than 5 % but less than 10 % (responders) and third group consisted of 7 males whose LVEF remained unchanged or worsened compared with pre-operative values (nonresponders). Prior to CRT, no statistically significant differences were found between groups in hemodynamic parameters (EF, EDV, ESV, SV), intra- and interventricular dyssynchrony, as well as in the midsize of perfusion defects. Following long-term CRT, we found increase in LVEF and decrease in average size of perfusion defects in groups of hyperresponders and responders (p < 0.05). Results of SPECT with (123)I-BMIPP, performed prior to CRT, showed that nonresponders had more pronounced disturbance of myocardial metabolism compared with the group of hyperresponders (20 vs. 14.7 %, p < 0.05). CONCLUSION: The radionuclide methods can be used as possible indicators in the evaluation effectiveness and selection of candidates on the CRT.

Comparison of simultaneous and sequential SPECT imaging for discrimination tasks in assessment of cardiac defects.

Simultaneous rest perfusion/fatty-acid metabolism studies have the potential to replace sequential rest/stress perfusion studies for the assessment of cardiac function. Simultaneous acquisition has the benefits of increased signal and lack of need for patient stress, but is complicated by cross-talk between the two radionuclide signals. We consider a simultaneous rest (99m)Tc-sestamibi/(123)I-BMIPP imaging protocol in place of the commonly used sequential rest/stress (99m)Tc-sestamibi protocol. The theoretical precision with which the severity of a cardiac defect and the transmural extent of infarct can be measured is computed for simultaneous and sequential SPECT imaging, and their performance is compared for discriminating (1) degrees of defect severity and (2) sub-endocardial from transmural defects. We consider cardiac infarcts for which reduced perfusion and metabolism are observed. From an information perspective, simultaneous imaging is found to yield comparable or improved performance compared with sequential imaging for discriminating both severity of defect and transmural extent of infarct, for three defects of differing location and size.

Quantitative simultaneous 99mTc/123I cardiac SPECT using MC-JOSEM.

Simultaneous rest 99mTc-Sestamibi/ 123I-BMIPP cardiac SPECT imaging has the potential to replace current clinical 99mTc-Sestamibi rest/stress imaging and therefore has great potential in the case of patients with chest pain presenting to the emergency department. Separation of images of these two radionuclides is difficult, however, because their emission energies are close. The authors previously developed a fast Monte Carlo (MC)-based joint ordered-subset expectation maximization (JOSEM) iterative reconstruction algorithm (MC-JOSEM), which simultaneously compensates for scatter and cross talk as well as detector response within the reconstruction algorithm. In this work, the authors evaluated the performance of MC-JOSEM in a realistic population of 99mTc/123I studies using cardiac phantom data on a Siemens e.cam system using a standard cardiac protocol. The authors also compared the performance of MC-JOSEM for estimation tasks to that of two other methods: standard OSEM using photopeak energy windows without scatter correction (NSC-OSEM) and standard OSEM using a Compton-scatter energy window for scatter correction (SC-OSEM). For each radionuclide the authors separately acquired high-count projections of radioactivity in the myocardium wall, liver, and soft tissue background compartments of a water-filled torso phantom, and they generated synthetic projections of various dual-radionuclide activity distributions. Images of different combinations of myocardium wall/background activity concentration ratios for each radionuclide were reconstructed by NSC-OSEM, SC-OSEM, and MC-JOSEM. For activity estimation in the myocardium wall, MC-JOSEM always produced the best relative bias and relative standard deviation compared with NSC-OSEM and SC-OSEM for all the activity combinations. On average, the relative biases after 100 iterations were 8.1% for 99mTc and 3.7% for 123I with MC-JOSEM, 39.4% for 99mTc and 23.7% for 123I with NSC-OSEM, and 20.9% for 99mTc with SC-OSEM. The relative standard deviations after 30 iterations were 0.7% for 99mTc and 1.0% for 123I with MC-JOSEM, as compared to 1.1% for 99mTc and 1.2% for 123I with NSC-OSEM and 1.3% for 99mTc with SC-OSEM. Finally, the authors compared the relative standard deviation after 30 iterations with the minimum theoretical variance on activity estimation, the Cramer-Rao lower bound (CRB), and with the biased CRB. The measured precision was larger than the biased bound values by factors of 2-4, suggesting that further improvement could be made to the method.

A cost effective non-commercial ECL-solution for Western blot detections yielding strong signals and low background.

We compared several alternative ECL solutions for Western blot detection of endogenous proteins in whole cell lysates using inexpensive, commercially available reagents. Starting from an existing protocol based on p-coumaric acid (pCA) as enhancer, we found that the ECL solution containing 4-iodophenylboronic acid (4IPBA) generated strong specific signals and low background chemiluminescence. We optimised the luminol, 4IPBA and hydrogenperoxide concentrations of this 4IPBA-ECL solution. The optimised 4IPBA-ECL solution (100 mM Tris/HCl pH 8.8, 1.25 mM luminol, 2 mM 4IPBA, 5.3 mM hydrogenperoxide) shows a greatly increased signal intensity compared to the initial pCA-ECL protocol and to some commercially available ECL solutions. In addition, the optimised 4IPBA-ECL solution also generates much lower background chemiluminescence than other non-commercial ECL solutions using p-coumaric acid or 4-iodophenol as enhancers. The 4IPBA-ECL solution was stable when stored but had the lowest background when prepared freshly from stock solutions. Thus, we present an optimised protocol for a well-performing inexpensive ECL solution which is an alternative to expensive commercial ECL solutions and which achieves a better signal and lower background than the commercial solutions tested.

Assessment of Takotsubo cardiomyopathy (transient left ventricular apical ballooning) using 99mTc-tetrofosmin, 123I-BMIPP, 123I-MIBG and 99mTc-PYP myocardial SPECT.

UNLABELLED: We compared Takotsubo cardiomyopathy (transient left ventricular apical ballooning) with acute myocardial infarction (AMI) using two-dimensional echocardiography, 99mTc-tetrofosmin, 99mTc-PYP, 123I-BMIPP and 123I-MIBG myocardial SPECT. METHODS: We examined 7 patients with Takotsubo cardiomyopathy and 7 with AMI at the time of emergency admission (acute phase), and 2-14 days (subacute phase), one month (chronic phase), and 3 months (chronic II phase) after the attack. The left ventricle was divided into nine regions on echocardiograms and SPECT images, and the degree of abnormalities in each region was scored according to five grades from normal (0) to severely abnormal (4). RESULTS: Coronary angiography showed the absence of stenotic regions in patients with Takotsubo cardiomyopathy, and severely stenotic and/or occlusive lesions in patients with AMI. The total ST segment elevation on electrocardiograms (mm) was 7.8 +/- 3.7 in those with Takotsubo cardiomyopathy, and 7.3 +/- 3.9 in patients with AMI. Abnormal wall motion scores on echocardiograms were 14.2 +/- 4.6, 4.7 +/- 4.0, 1.7 +/- 2.0 and 0.5 +/- 0.4 during the acute, subacute, chronic and chronic II phases, respectively, in patients with Takotsubo cardiomyopathy, and 14.0 +/- 4.3, 11.4 +/- 3.9, 8.8 +/- 3.6 and 5.2 +/- 4.8 in those with AMI. Abnormal myocardial perfusion scores on 99mTc-tetrofosmin images were 11.8 +/- 3.5, 3.2 +/- 3.0, 0.5 +/- 1.2 and 0.2 +/- 0.4 during the acute, subacute, chronic and chronic II phases, in patients with Takotsubo cardiomyopathy, and 16.2 +/- 4.3, 13.9 +/- 4.6, 7.9 +/- 4.6 and 5.0 +/- 4.5, respectively, in those with AMI. Abnormal myocardial fatty acid scores on 123I-BMIPP images were 12.6 +/- 3.7, 6.8 +/- 3.2 and 0.4 +/- 0.6 during the subacute, chronic and chronic II phases, respectively, in patients with Takotsubo cardiomyopathy, and 16.5 +/- 5.1, 14.7 +/- 4.8 and 7.5 +/- 4.5 in those with AMI. Abnormal myocardial sympathetic nerve function scores on 123I-MIBG images were 14.8 +/- 4.0, 8.8 +/- 4.0 and 0.4 +/- 0.6 during the subacute, chronic, chronic II phases, respectively, in patients with Takotsubo cardiomyopathy, and 18.6 +/- 6.5, 16.8 +/- 6.8 and 12.9 +/- 5.2 in those with AMI. Myocardial 99mTc-PYP uptake was abnormal not only in patients with AMI but also in those with Takotsubo cardiomyopathy during the acute phase. CONCLUSIONS: Takotsubo cardiomyopathy might represent a stunned myocardium caused by a disturbance of the coronary microcirculation.

[Assessment of the time course of stunned myocardium with cardiac magnetic resonance imaging: a case report].

A 77-year-old woman with chest pain was admitted to our hospital for evaluation and treatment. Electrocardiography showed T-wave inversion in the I, aVL and V2-V6 leads. Emergency coronary angiography showed 75% stenosis in the left anterior descending artery. Left ventriculography demonstrated akinesis of the left ventricular apical region. Iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid radioactive isotope imaging showed an uptake defect in the apical region during the acute phase, but the defect disappeared 1 month later. Cine cardiac magnetic resonance (CMR) in the acute phase showed apical akinesis and hyperkinesis of the mid region, as observed by left ventriculography. Contrast magnetic resonance imaging with gadolinium showed no delayed hyperenhancement. One month later, cine CMR showed disappearance of the abnormal wall motion and contrast magnetic resonance imaging demonstrated no delayed hyperenhancement. CMR is useful to monitor changes in wall motion and wall thickening in the stunned myocardium.

Latent abnormal fatty acid metabolism in apparently normal perfusion during stress in patients with restenosis after coronary angioplasty: assessment by exercise stress thallium-201 and iodine-123-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid-dual myocardial single-photon emission computed tomography.

Restenosis is a major problem in patients undergoing coronary angioplasty. Reduced uptake of iodine-123-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (I-BMIPP-123) relatively to thallium-201 (Tl-201) has been attributed to the metabolic damage in the myocardium in patients with coronary artery disease. Therefore, we performed exercise stress Tl-201 and I-BMIPP-123 dual myocardial single-photon emission computed tomography (SPECT) to detect coronary restenosis in 48 patients (35 men and 13 women, mean age 66 +/- 8 years), followed by coronary angiography at follow-up. Patients were divided into 2 groups: those with (n = 24) and without (n = 24) restenosis. Redistribution of Tl-201 was seen more frequently in the restenosis group than in no-restenosis group (58% [14 of 24] vs 8% [2 of 24], p <0.05). Five of 10 patients (50%) with restenosis but without Tl-201 redistribution had Tl-201/I-BMIPP-123 discrepancy during stress. In patients without restenosis, only 1 patient had this discrepancy during stress. Incorporation of Tl-201/I-BMIPP-123 uptake discrepancy during stress significantly improved the sensitivity (58% [14 of 24] to 79% [19 of 24]) with preserved specificity (92% [22 of 24] to 88% [21 of 24]). Exercise stress Tl-201 and I-BMIPP-123 dual myocardial SPECT revealed that latent abnormal fatty acid metabolism may exist in apparently normal perfusion during stress in patients with restenosis after coronary angioplasty. Use of I-BMIPP-123 together with Tl-201 during stress SPECT substantially improved the diagnostic accuracy of restenosis based on Tl-201 redistribution (from 75% to 83%).

Assessment of fatty acid metabolism in taxan-induced myocardial damage with iodine-123 BMIPP SPECT: comparative study with myocardial perfusion, left ventricular function, and histopathological findings.

UNLABELLED: We investigated myocardial fatty acid metabolism in taxan-induced myocardial damage in patients with advanced lung cancer. PATIENTS AND METHODS: Twenty-five patients with non-small-cell lung cancer were treated with taxan combined with carboplatin intravenously for three cycles. Myocardial SPECT imaging using 99mTc-methoxyisobutyl isonitrile (MIBI) and 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was performed successively before and after chemotherapy. Regional uptake scores of BMIPP and MIBI were visually assessed and total uptake scores and the number of abnormal segments were calculated. Left ventricular ejection fraction (LVEF) was obtained by first-pass radionuclide angiocardiography using MIBI. Postmortem pathological examination was performed in 5 patients. RESULTS: Total BMIPP uptake scores after chemotherapy were significantly lower than those before chemotherapy (23.4 +/- 3.4 vs. 26.6 +/- 0.8; p < 0.001). Mean LVEF showed a significant decrease after chemotherapy. Of the 25 patients, 4 exhibited a decrease in LVEF of more than 10%, 1 had a decrease in LVEF to below 50%, and 1 developed congestive heart failure. These 6 patients had significant decreases in total BMIPP uptake scores and increases in the number of abnormal segments as compared with the other 19 patients. Histopathological examination of myocardial tissue showed interstitial edema and disarrayed myocardial cells. CONCLUSION: Taxan impairs myocardial fatty acid metabolism. 123I-BMIPP myocardial SPECT is useful for evaluating the cardiotoxicity induced by taxan.

[Assessment of microcirculation disturbance with nuclear cardiology in a patient with coronary ectasia: a case report].

A 69-year-old woman presented with dyspnea on exertion. Echocardiography showed dilatation and diffuse hypokinesis of the left ventricle. 99mTc-tetrofosmin myocardial SPECT showed moderately reduced uptake in the anteroseptal wall and the inferior wall on the rest images, but was improved on the ATP loading images. 123I-BMIPP myocardial SPECT showed severely reduced uptake in the anterior wall and the inferior wall. These SPECT findings suggested ischemic heart disease rather than dilated cardiomyopathy. Coronary angiography showed no organic stenosis, but diffuse coronary ectasia was noted in three vessels. Intravascular ultrasound revealed remarkable coronary ectasia, with a maximal diameter of 8.2 mm. Coronary flow velocity as measured by Doppler blood flow guide wire was remarkably reduced. Coronary spasms were not provocated by ergonovine loading test. These findings suggested that microvascular thrombi and disturbance of dilatation caused myocardial ischemia in this patient. We treated the patient with ticlopidine and nicorandil. Following treatment left ventricle wall motion, 99mTc-tetrofosmin and 123I-BMIPP myocardial SPECT findings were improved.

Quantitative assessment of the total myocardial uptake ratio of 123I-BMIPP by using the Ishii-MacIntyre method is useful for predicting cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy.

We evaluated the usefulness of the total myocardial uptake ratio (TMUR) of 15-(p-[123I]iodophenyl)-3(R,S)-methyl-pentadecanoic acid (123I-BMIPP) for predicting cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy. Six patients with mitochondrial encephalomyopathy, four with myotonic dystrophy, and 10 control subjects were studied. Quantitative assessment of 123I-BMIPP dynamic myocardial imaging was performed, and the TMUR of 123I-BMIPP was calculated according to the Ishii-MacIntyre method. Then, the TMUR was compared in the 10 patients and 10 healthy controls, and all patients were followed for 56.1+/-22.1 months to evaluate cardiac complications. TMUR in patients (2.69+/-0.64) was significantly (P =0.01) lower than that in controls (3.28+/-0.25). Three patients in whom the TMUR value was above 3.00 had no cardiac complications. On the other hand, all patients in whom TMUR was below 3.00 had some kind of cardiac complication during the follow-up period. Two patients showed progressive conduction abnormality and underwent pacemaker implantation, one patient had sick sinus syndrome and underwent pacemaker implantation, another patient showed non-sustained ventricular tachycardia and paroxysmal atrial fibrillation, and four of seven patients, including one with a pacemaker, showed an increased cardiothoracic ratio value over 50%. In conclusion, measurement of the TMUR by the Ishii-MacIntyre method is useful for evaluating the development of cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy.

[Assessment of therapeutic effect in acute myocardial infarction using early/delayed images of 123I-BMIPP myocardial scintigraphy].

This study was aimed at analyzing the discordance between the initial and late scintigraphic images in patients with acute myocardial infarction (AMI), and utilizing the data obtained for the treatment of AMI patients. Ninety-one patients with a history of the first episode of AMI were enrolled as subjects for this study. Emergency coronary angiography was performed in all the patients and left ventriculography (LVG) was carried out subsequently. 123I-BMIPP myocardial scintigraphy was performed to obtain initial images (BMi) and delayed images at 4 hours (BMd). Scintigraphy was performed a mean of 6 days after the onset of AMI in the patients. The subjects were classified into three groups according to the scintigraphic data. Quantitative gated single photon emission computed tomography (SPECT) with 99mTc-sestamibi (MIBI) was also conducted one month and 6 months later in all the patients. Discordance was observed in 51% of the patients. Left ventricular volume based on the quantitative gated SPECT (QGS) data at one month and 6 months after myocardial scintigraphy was significantly smaller in the washout group than in the other two groups. There was no significant change in LV volume measured at 6 months as compared to that measured at one month in the washout group. Significant increases in LVEDVI and LVESVI were observed over time in the no discordance group. In the fill-in group, the LV volume at one month was significantly higher than that in the washout group, but no significant change with time was observed. During the subacute stage of myocardial infarction, discordance is often seen between initial and late BMIPP-myocardial-scintigraphic images. The presence of such discordance, and analysis of its pattern, may be useful in predicting the cardiac function in these patients during the chronic phase of this disease.

Differences in fatty acid metabolic disorder between ischemic myocardium and doxorubicin-induced myocardial damage: assessment using BMIPP dynamic SPECT with analysis by the Rutland method.

UNLABELLED: Dynamic myocardial SPECT data acquired with 15-(123)I-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) were analyzed by the Rutland method. The relative time-activity curves generated from dynamic SPECT in normal control subjects were compared with similar curves from patients with established ischemic heart disease (IHD) and doxorubicin-induced myocardial damage (DxMD). Comparison of such time-activity curves may provide some indirect information concerning qualitative differences in BMIPP metabolism. METHODS: Thirteen patients with various malignancies who received doxorubicin, 16 patients with IHD, and 15 normal control subjects were examined. Immediately after the bolus injection of BMIPP, dynamic data acquisition with a 3-head SPECT system was started and continued for 15 min. Using the time-activity curves of the myocardium as the output function (Mo(t)) and the time-activity curves of the left ventricular cavity as the input function (B(t)), the Rutland equation was calculated: Mo(t)/B(t) = F + K integral B(t)dt/B(t), where F is the blood - background subtraction factor and K is the uptake constant. The duration of the linear portion in this equation and the K values were evaluated. RESULTS: Mo(t)/B(t) was plotted against integral B(t)dt/B(t). Mo(t)/B(t) showed a good linear correlation with integral B(t)dt/B(t) from 30 s to 230 +/- 57 s in normal control subjects. The duration of this linearity was prolonged to 317 +/- 79 s in DxMD (P = 0.0014) and shortened to 182 +/- 58 s in IHD (P = 0.039). The mean K value was 0.0740 +/- 0.0184 in normal control subjects, significantly higher than the K values of 0.0599 +/- 0.0148 in DxMD patients (P = 0.026) and 0.0497 +/- 0.0189 (P = 0.0020) in IHD patients. CONCLUSION: Analysis of BMIPP dynamic SPECT data by the Rutland method is useful for detecting qualitative differences in BMIPP metabolism in various types of myocardial damage. It is speculated that the fatty acid metabolic disorder is characterized by a delay in metabolism in DxMD and by increased backdiffusion in IHD.

Scintigraphic assessment of patients with electrocardiographic left ventricular hypertrophy with ST-T changes without apparent cause.

PURPOSE: Some patients who show electrocardiographic left ventricular hypertrophy with ST-T changes (ECG-LVH) are difficult to evaluate using routine examinations. To clarify the pathologic process in these patients, the authors performed several scintigraphic examinations. MATERIALS AND METHODS: Twenty-nine patients with ECG-LVH, without apparent cause, such as left ventricular (LV) systolic overloading or increased LV mass, were examined by myocardial I-123 MIBG imaging, I-123 BMIPP imaging, and exercise-induced stress perfusion imaging. In addition to the visual assessment of each image, we calculated global and regional myocardial washout of I-123 MIBG (%washout). The LV was assessed using conventional echocardiography. RESULTS: Visually observed abnormalities were located exclusively at the LV apex with all imaging methods and were detected in 76%, 52%, and 17% of patients by I-123 MIBG, I-123 BMIPP, and perfusion imaging, respectively. A follow-up study revealed that the apical defects of I-123 MIBG were subsequently followed by defects of I-123 BMIPP and then perfusion abnormalities. In patients with an apical defect revealed by I-123 MIBG imaging, apical %washout was high. In nine patients who underwent myocardial biopsy, myocardial disarray was observed at the apical regions. CONCLUSIONS: In many patients with ECG-LVH without apparent cause, sympathetic abnormalities are observed at the apex, similar to pathologic changes in hypertrophic cardiomyopathy. These abnormalities may lead to changes in fatty acid metabolism and perfusion.