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Myocardial perfusion imaging (MPI) provides physiologic and functional information about the heart muscle and its blood flow. Extracardiac radioactivity can interfere with visualization of the inferior wall of the myocardium, leading to poor-quality images, difficulties in interpretation, and delays in routine practice. This study aimed to identify the efficiency of having the patient consume a carbonated lemon drink to minimize the extracardiac radioactivity of 99mTc-sestamibi in comparison to 99mTc-tetrofosmin during MPI. Methods: This was a retrospective study that recruited 158 patients with known or suspected coronary artery disease referred to undergo 99mTc-sestamibi or 99mTc-tetrofosmin rest/stress single-day MPI. The patients were divided into 2 groups of mixed sexes and different ages. The first group comprised 78 patients injected with 99mTc-sestamibi, and the second group comprised 80 patients injected with 99mTc-tetrofosmin. For both groups, the patients drank 30 mL of fresh lemon juice diluted with 150 mL of soda water, and then we gave the patients about 100 mL of straight soda water, before imaging for both the rest and the stress phases. Results: Generally, in both groups, the 99mTc-tetrofosmin produced a good-quality image in comparison with the 99mTc-sestamibi. The mean rank of the total score for 99mTc-tetrofosmin (62.75) was less than that for 99mTc-sestamibi (96.68), and this difference was highly statistically significant (P = 0.000). There were statistically significant differences in the ratios and mean ranks for both groups in favor of 99mTc-tetrofosmin in patients having coronary artery disease. Conclusion: The use of a carbonated lemon drink minimizes extracardiac activity from both 99mTc-labeled MPI radiopharmaceuticals. This finding was more statistically significant for 99mTc-tetrofosmin MPI, providing better image quality and earlier imaging in both the rest and the stress phases because of faster hepatobiliary clearance. [ABSTRACT FROM AUTHOR]

BackgroundSPECT myocardial perfusion imaging (MPI) is a clinical mainstay that is typically performed with static imaging protocols and visually or semi-quantitatively assessed for perfusion defects based upon the relative intensity of myocardial regions. Dynamic cardiac SPECT presents a new imaging technique based on time-varying information of radiotracer distribution, which permits the evaluation of regional myocardial blood flow (MBF) and coronary flow reserve (CFR). In this work, a preliminary feasibility study was conducted in a small patient sample designed to implement a unique combined static-dynamic single-dose one-day visit imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT for improving the diagnosis of coronary artery disease (CAD).MethodsFifteen patients (11 males, four females, mean age 71 ± 9 years) were enrolled for a combined dynamic and static SPECT (Infinia Hawkeye 4, GE Healthcare) imaging protocol with a single dose of 99mTc-tetrofosmin administered at rest and a single dose administered at stress in a one-day visit. Out of 15 patients, eleven had selective coronary angiography (SCA), 8 within 6 months and the rest within 24 months of SPECT imaging, without intervening symptoms or interventions. The extent and severity of perfusion defects in each myocardial region was graded visually. Dynamically acquired data were also used to estimate the MBF and CFR. Both visually graded images and estimated CFR were tested against SCA as a reference to evaluate the validity of the methods.ResultsOverall, conventional static SPECT was normal in ten patients and abnormal in five patients, dynamic SPECT was normal in 12 patients and abnormal in three patients, and CFR from dynamic SPECT was normal in nine patients and abnormal in six patients. Among those 11 patients with SCA, conventional SPECT was normal in 5, 3 with documented CAD on SCA with an overall accuracy of 64%, sensitivity of 40% and specificity of 83%. Dynamic SPECT image analysis also produced a similar accuracy, sensitivity, and specificity. CFR was normal in 6, each with CAD on SCA with an overall accuracy of 91%, sensitivity of 80%, and specificity of 100%. The mean CFR was significantly lower for SCA detected abnormal than for normal patients (3.86±1.06 vs 1.94±0. 0.67, P

Abstract Background Quantitative SPECT enables absolute quantification of uptake in perfusion defects. The aim of this experimental study is to assess quantitative accuracy and precision of a novel iterative reconstruction technique (Evolution; GE Healthcare) for the potential application of response monitoring using 99mTc-tetrofosmin SPECT/CT in patients with coronary artery disease (CAD). Methods Acquisitions of an anthropomorphic torso phantom with cardiac insert containing defects (with varying sizes), filled with 99mTc-pertechnetate, were performed on a SPECT/CT (Discovery 670 Pro, GE Healthcare). Subsequently, volumes of interest of the defects were manually drawn on CT to assess the recovery coefficient (RC). Bull’s eye plots were composed to evaluate the uptake per segment. Finally, 99mTc-tetrofosmin SPECT/CT scans of 10 CAD patients were used to illustrate clinical application. Results The phantom study indicated that Evolution showed convergence after 7 iterations and 10 subsets. The average repeatability deviation of all configurations was 2.91% and 3.15% (%SD mean) for filtered (Butterworth) and unfiltered data, respectively. The accuracy after post-filtering was lower compared to the unfiltered data with a mean (SD) RC of 0.63 (0.05) and 0.70 (0.07), respectively (p < 0.05). More artificial defects were found on Bull’s eye plots created with the unfiltered data compared to filtered data. Eight out of ten patients showed significant changes in uptake before and after treatment (p < 0.05). Conclusion Quantification of 99mTc-tetrofosmin SPECT/CT seems feasible for CAD patients when 7 iterations (10 subsets), Butterworth post-filtering (cut off frequency 0.52 in cycles/cm, order of 5) and manual CT-delineation are applied. However, future prospective patient studies are required for clinical application.

Background: Left ventricular mechanical dyssynchrony (LVMD) induced by exercise stress was reported to be clinically useful in detecting multivessel coronary artery diseases. The aim of this study was to compare the prognostic value of LVMD induced by pharmacological stress with that induced by exercise stress. Methods: We retrospectively examined 918 consecutive patients who underwent exercise (N = 310) or pharmacological stress (N = 608) 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) with normal myocardial perfusion. LVMD was evaluated by phase analysis as the indices of phase bandwidth and phase standard deviation (PSD). Results: During the follow-up period (2.2 ± 1.9 years), 74 major cardiac events (MCEs) occurred (7 cases of cardiac death, 17 cases of heart failure, and 50 cases of coronary intervention). In global patients, the indices of LVMD on rest images were significantly greater in patients with MCEs (bandwidth (°): 51 ± 31 vs 37 ± 21, P =.001, PSD: 14 ± 9 vs 10 ± 6, P =.001). The exercise stress bandwidth was significantly higher in patients with MCEs (62 ± 37° vs 42 ± 21°, P =.026), as was the pharmacological stress bandwidth (57 ± 35° vs 43 ± 24°, P =.006). Multivariate analysis demonstrated the exercise stress bandwidth to be an independent predictor of MCEs (HR 1.017, CI 1.003 to 1.032, P =.019), but the pharmacological stress bandwidth had no influence on MCEs. Conclusions: LVMD induced by exercise stress was an independent predictor of MCEs in patients with normal perfusion SPECT, whereas that induced by pharmacological stress had no association with further events. [ABSTRACT FROM AUTHOR]

Background: Quantitative SPECT enables absolute quantification of uptake in perfusion defects. The aim of this experimental study is to assess quantitative accuracy and precision of a novel iterative reconstruction technique (Evolution; GE Healthcare) for the potential application of response monitoring using 99mTc-tetrofosmin SPECT/CT in patients with coronary artery disease (CAD). Methods: Acquisitions of an anthropomorphic torso phantom with cardiac insert containing defects (with varying sizes), filled with 99mTc-pertechnetate, were performed on a SPECT/CT (Discovery 670 Pro, GE Healthcare). Subsequently, volumes of interest of the defects were manually drawn on CT to assess the recovery coefficient (RC). Bull's eye plots were composed to evaluate the uptake per segment. Finally, 99mTc-tetrofosmin SPECT/CT scans of 10 CAD patients were used to illustrate clinical application. Results: The phantom study indicated that Evolution showed convergence after 7 iterations and 10 subsets. The average repeatability deviation of all configurations was 2.91% and 3.15% (%SD mean) for filtered (Butterworth) and unfiltered data, respectively. The accuracy after post-filtering was lower compared to the unfiltered data with a mean (SD) RC of 0.63 (0.05) and 0.70 (0.07), respectively (p < 0.05). More artificial defects were found on Bull's eye plots created with the unfiltered data compared to filtered data. Eight out of ten patients showed significant changes in uptake before and after treatment (p < 0.05). Conclusion: Quantification of 99mTc-tetrofosmin SPECT/CT seems feasible for CAD patients when 7 iterations (10 subsets), Butterworth post-filtering (cut off frequency 0.52 in cycles/cm, order of 5) and manual CT-delineation are applied. However, future prospective patient studies are required for clinical application. [ABSTRACT FROM AUTHOR]

Background: An assessment of cardiac events and survival using quantitative gated myocardial single-photon emission computed tomography (SPECT) (J-ACCESS) associated several risk factors with cardiac events in Japan. The clinical course after revascularization and/or optimal medical therapy (OMT) was followed in patients with coronary artery disease (CAD) at moderate-to-high risk estimated by software incorporating the J-ACCESS risk model. The present study aimed to determine the relevance of changes in estimated risk to outcomes of these therapies. Methods: This study included 494 patients with possible or definite CAD who underwent initial pharmacological stress 99mTc-tetrofosmin myocardial perfusion SPECT (MPS) before and eight months after therapy. Major cardiac event risk during 3 years of follow-up was calculated using an equation based on that in the J-ACCESS study. Patients with ≥ 10% cardiac event risk estimated at the first MPS (n = 31) were analyzed and followed up for at least 1 year. Results: Estimated risk was reduced by ≥ 5% in 14 patients (45%) after therapy. During a follow-up period of 22.1 ± 6.7 months, one patient without such reduction had a major cardiac event. Mean %summed stress scores significantly decreased from baseline to follow-up in patients with and without risk reduction. Left ventricular ejection fraction (LVEF [%]) at rest was significantly increased at the second, compared with the first MPS between patients with, than without risk reduction (57 ± 17 vs. 45 ± 16%, p = 0.001 and 50 ± 11 vs. 49 ± 9%, p = 0.953, respectively). Conclusions: A reduction in cardiac ischemia and an increase in LVEF by revascularization and/or OMT were necessary to avoid cardiac events among patients with moderate-to-high estimated risk, and changes in event risk were quantifiable. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of coronary artery disease (CAD) is high in patients with diabetes. Because ischemia and infarction are often silent in diabetic patients, diagnosis of CAD occurs inevitably late. It is essential to identify the presence of CAD in diabetic patients to start early treatment. Therefore, the aim of this study was to determine the prevalence of abnormal myocardial perfusion in asymptomatic type 2 diabetic patients using myocardial perfusion imaging. Methods: Fifty-nine patients with type 2 diabetes, who did not have any history of CAD, but did have risk factors underwent myocardial perfusion single-photon emission computed tomography (SPECT) imaging using 99mTc-tetrofosmin and a 2-day stress–rest protocol. Two nuclear medicine specialists independently interpreted the images. Statistical analysis was performed to determine if there is a correlation between the presence of perfusion abnormalities and the history of diabetes (duration of disease, type of treatment, level of control, and presence and type of complications). The influence of other factors such as age, sex, smoking history, and family history of CAD, with abnormal scans were also studied. Results: Of the 59 patients, abnormal scans were detected in 22 (37%) including 16 with reversible defects due to stress-induced ischemia. Hence the prevalence was 37%. Duration of diabetes, use of insulin, nephropathy, and neuropathy were significantly associated with abnormal scans (p = 0.048, p = 0.045, p = 0.006, and p = 0.03, respectively). Additionally, positive family history of CAD was highly associated with perfusion abnormalities (p

The accumulation of high levels of 99mTc-tetrofosmin (99mTc-TF) in the hepatobiliary system can lead to imaging artifacts and interference with diagnosis. The present study investigated the transport mechanisms of 99mTc-TF and attempted to apply competitive inhibition using a specific inhibitor to reduce 99mTc-TF hepatic accumulation. In this in vitro study, 99mTc-TF was incubated in HEK293 cells expressing human organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP2B1, organic anion transporter 2 (OAT2), organic cation transporter 1 (OCT1), OCT2, and Na+-taurocholate cotransporting polypeptide with or without each specific inhibitor to evaluate the contribution of each transporter to 99mTc-TF transportation. In vivo studies, dynamic planar imaging, and single photon emission computed tomography (SPECT) experiments with rats were performed to observe alterations to 99mTc-TF pharmacokinetics using cimetidine (CMT) as an OCT1 inhibitor. Time–activity curves in the liver and heart were acquired from dynamic data, and the 99mTc-TF uptake ratio was calculated from SPECT. From the in vitro study, 99mTc-TF was found to be transported by OCT1 and OCT2. When CMT-preloaded rats and control rats were compared, the hepatic accumulation of the 99mTc-TF was reduced, and the time to peak heart count shifted to an earlier stage. The hepatic accumulation of 99mTc-TF was markedly suppressed, and the heart-to-liver ratio increased 1.6-fold. The pharmacokinetics of 99mTc-TF were greatly changed by OCT1 inhibitor. Even in humans, the administration of OCT1 inhibitor before cardiac SPECT examination may reduce 99mTc-TF hepatic accumulation and contribute to the suppression of artifacts and the improvement of SPECT image quality.

Considered rare disease in the past, primary hyperparathyroidism (PHPT) has dramatically increased in incidence over the past thirty years with the introduction of routine calcium measurements; it is now approximately 42 per 100 000 persons. By far, the most common lesion found in patients with PHPT is the solitary parathyroid adenoma, occurring in 85%-90% of patients, while in the rest 10%- 15% primary hyperplasia of the parathyroid glands is present. Currently, the most widely used surgical approach is minimally invasive parathyroidectomy which is associated with less post-surgery complications and shorter operation time. To be successful this procedure needs to rely on a precise preoperative localization of the abnormal parathyroid glands, hence preoperative parathyroid imaging gained so large importance. The rationale for locating abnormal parathyroid tissue prior to surgery is that the glands can be notoriously unpredictable in their location. There is a general consensus that the best imaging procedure identifying abnormal parathyroid glands is the preoperative scintigraphy with 99mTc-sestamibi or 99mTc-tetrofosmin. It is characterized with high sensitivity and specificity exceeding those of ultrasound, CT or MRI. Combining scintigraphy with the other imaging techniques increases the precision for topic localization.

Objective(s): Use of a positron emission tomography (PET)/single-photonemission computed tomography (SPECT) system facilitates the simultaneousacquisition of images with fluorine-18 fluorodeoxyglucose (18F-FDG) andtechnetium (99mTc)-tetrofosmin. However, 18F has a short half-life, and 511keV Compton-scattered photons are detected in the 99mTc energy window.Therefore, in this study, we aimed to investigate the consequences of thesefacts.Methods: The crosstalk correction for images in the 99mTc energy windowinvolved the dual energy window (DEW) subtraction method. In phantomstudies, changes in the count of uniform parts in a phantom (due to attenuationfrom decay), signal detectability in the hot-rod part of the phantom, and thedefect contrast ratio in a cardiac phantom were examined.Results: For 18F-FDG in the step-and-shoot mode, nearly a 9% difference wasobserved in the count of projection data between the start and end positionsof acquisition in the uniform part of the phantom. Based on the findings,the detectability of 12 mm hot rods was relatively poor. In the continuousacquisition mode, the count difference was corrected, and detectability of thehot rods was improved. The crosstalk from 18F to the 99mTc energy windowwas approximately 13%. In the cardiac phantom, the defect contrast in 99mTcimages from simultaneous dual-radionuclide acquisition was improved byapproximately 9% after DEW correction; the contrast after correction wassimilar to acquisition with 99mTc alone.Conclusion: Based on the findings, the continuous mode is useful for 18F-FDGacquisition, and DEW crosstalk correction is necessary for 99mTc-tetrofosminimaging.

Purpose: In this prospective study we compared the accuracy of 18F-fluorocholine PET/CT with that of 99mTc-MIBI or99mTc-tetrofosmin SPECT/CT in the preoperative detection of parathyroid adenoma in patients with primary hyperparathyroidism. We also assessed the value of semiquantitative parameters in differentiating between parathyroid hyperplasia and adenoma.Methods: Both 18F-fluorocholine PET/CT and 99mTc-MIBI/tetrofosmin SPECT/CT were performed in 100 consecutive patients with biochemical evidence of primary hyperparathyroidism. At least one abnormal focus on either 18F-fluorocholine or 99mTc-MIBI/tetrofosmin corresponding to a parathyroid gland or ectopic parathyroid tissue was considered as a positive finding. In 76 patients with positive findings on at least one imaging modality, surgical exploration was performed within 6 months, and the results were related to histopathological findings and clinical and laboratory findings at 3-6 months as the standard of truth. In 24 patients, no surgery was performed: in 18 patients with positive imaging findings surgery was refused or considered risky, and in 6 patients imaging was negative. Therefore, data from 82 patients (76 undergoing surgery, 6 without surgery) in whom the standard of truth criteria were met, were used in the final analysis.Results: All patients showed biochemical evidence of primary hyperparathyroidism with a mean serum calcium level of 2.78 ± 0.34 mmol/l and parathormone (PTH) level of 196.5 ± 236.4 pg/ml. The study results in 76 patients with verified histopathology and 3 patients with negative imaging findings were analysed. Three of six patients with negative imaging showed normalized serum PTH and calcium levels on laboratory follow-up at 3 and 6 months, and the results were considered true negative. In a patient-based analysis, the detection rate with 18F-fluorocholine PET/CT was 93% (76/82), but was only 61% (50/82) with 99mTc-MIBI/tetrofosmin SPECT/CT. In a lesion-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of 18F-fluorocholine PET/CT in the detection of parathyroid adenoma were 93.7%, 96.0%, 90.2%, 97.4% and 95.3%, respectively, and of 99mTc-MIBI/tetrofosmin SPECT/CT were 60.8%, 98.5%, 94.1%, 86.3% and 87.7%, respectively. Although 18F-fluorocholine PET-positive adenomatous lesions showed higher SUVmax values than the hyperplastic glands (6.80 ± 3.78 vs. 4.53 ± 0.40) in the semiquantitative analysis, the difference was not significant (p = 0.236). The mean size (measured as the length of the greatest dimension) and weight of adenomas were 15.9 ± 7.6 mm (median 15 mm, range 1-40 mm) and 1.71 ± 1.86 g (median 1 g, range: 0.25-9 g), respectively. Among the analysed parameters including serum calcium and PTH and the size and weight of parathyroid adenomas, size was significantly different between patients with negative 99mTc-MIBI/tetrofosmin SPECT/CT and those with positive 99mTc-MIBI/tetrofosmin SPECT/CT (mean size 13.4 ± 7.6 mm vs. 16.9 ± 7.4 mm, respectively; p = 0.042).Conclusion: In this prospective study, 18F-fluorocholine PET/CT showed promise as a functional imaging modality, being clearly superior to 99mTc-MIBI/tetrofosmin SPECT/CT, especially in the detection and localization of small parathyroid adenomas in patients with primary hyperparathyroidism. SUVmax was higher in parathyroid adenomas than in hyperplasia. However, further evaluation of this modality is needed. [ABSTRACT FROM AUTHOR]

Background: Dobutamine stress myocardial perfusion imaging (MPI) is a useful alternative for the evaluation of coronary artery disease (CAD) in elderly patients who are unable to perform an exercise stress test. However, data on the long-term prognostic value of stress MPI in elderly patients are lacking. Therefore, this study evaluated the long-term prognostic value of dobutamine stress MPI in elderly patients unable to perform an exercise test.Methods: The study population consisted of 247 elderly patients (mean age 71 ± 5 years) who underwent dobutamine stress single-photon emission computed tomography (SPECT) MPI. An abnormal SPECT study was defined as the presence of fixed and/or reversible perfusion defects. A summed stress score (SSS) was obtained to estimate the extent and severity of perfusion defects. End points during follow-up were all-cause mortality, cardiac mortality, and nonfatal myocardial infarction (MI).Results: During a median follow-up of 14 years (range 12-16), 168 (68%) patients died (all-cause mortality), of which 56 (23%) were due to cardiac causes. Nonfatal MI occurred in 19 (8%) patients. Kaplan-Meier survival curves showed that MPI provided optimal risk stratification in patients with normal and abnormal MPI. Multivariable analysis identified an abnormal MPI as a strong significant predictor of all-cause mortality and cardiac events. A multivariable analysis also revealed that a reversible defect and SSS were strong long-term predictors of cardiac mortality and hard cardiac events.Conclusion: Dobutamine stress 99mTc-tetrofosmin SPECT provides incremental prognostic information for the prediction of long-term cardiovascular outcomes in elderly patients, unable to perform exercise testing. Dobutamine stress MPI is useful in risk classifying elderly patients. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to define reference values for left ventricular systolic synchrony and for the volume parameters of the left ventricle using myocardial perfusion SPECT-derived phase analysis method. Methods We evaluated data of 433 patients who underwent myocardial perfusion SPECT/CT during January 2012-February 2013 in Kuopio University Hospital. The final study population consisted of 52 patients (aged 42-84 years) who met the criteria: (1) no previously diagnosed cardiac disease, (2) normal ECG at rest, (3) no advanced coronary artery disease in CT and 4) normal myocardial perfusion in stress/rest myocardial perfusion SPECT/CT. The severity of mechanical dyssynchrony was assessed by phase analysis of gated myocardial SPECT at stress stage after pharmacological exercise and at rest using Quantitative Gated SPECT (QGS) software. Volume parameters of the left ventricle were also assessed. Results The phase histogram bandwidth at rest was 28.0 [63.7] degrees (median [95th percentile]). The standard deviation of phase histogram at rest was 7.8 [26.5] degrees. Entropy at the rest study was 54.0 [63.7] %. All left ventricular dyssynchrony parameters were statistically significantly higher at stress compared to rest. There were no statistically significant differences in dyssynchrony values between men and women. In volume parameters, reference values in male were expectedly higher than in female. Cardiac output did not differ significantly between genders. Conclusion In subjects without signs of cardiac diseases, the left ventricular systolic function is well synchronized. Phase analysis measurement does not depend on gender, age, BMI or blood pressure, but the values of dyssynchrony parameters increase during pharmacological stress. [ABSTRACT FROM AUTHOR]

99mTc-tetrofosmin (99mTc-TF) is a single-photon emission computed tomography tracer that has been used for brain tumor imaging. The aim of the study was to assess if 99mTc-TF uptake by glioblastoma cells correlates with their response to temozolomide (TMZ). We investigated the correlation of TMZ antitumor effect with the 99mTc-TF uptake in two glioblastoma cell lines. The U251MG cell line is sensitive to TMZ, whereas T98G is resistant. Viability and proliferation of the cells were examined by trypan blue exclusion assay and xCELLigence system. Cell cycle was analyzed with flow cytometry. The radioactivity in the cellular lysate was measured with a gamma scintillation counter. TMZ induced G2/M cell cycle arrest in U251MG cells, whereas there was no effect on cell cycle in T98G cells. Lower 99mTc-TF uptake was observed in U251MG cells that were exposed to TMZ compared to control (P = 0.0159). No significant difference in respect to 99mTc-TF uptake was found in T98G cells when exposed to TMZ compared to control (P = 0.8). With 99mTc-TF, it was possible to distinguish between TMZ-sensitive and resistant glioblastoma cells within 6 h of treatment initiation. Thus, 99mTc-TF uptake may consist a novel approach to assess an early response of glioblastoma to chemotherapy and deserves further investigation. [ABSTRACT FROM AUTHOR]

Objective(s): Use of a positron emission tomography (PET)/single-photon emission computed tomography (SPECT) system facilitates the simultaneous acquisition of images with fluorine-18 fluorodeoxyglucose (18F-FDG) and technetium (99mTc)-tetrofosmin. However, 18F has a short half-life, and 511 keV Compton-scattered photons are detected in the 99mTc energy window. Therefore, in this study, we aimed to investigate the consequences of these facts. Methods: The crosstalk correction for images in the 99mTc energy window involved the dual energy window (DEW) subtraction method. In phantom studies, changes in the count of uniform parts in a phantom (due to attenuation from decay), signal detectability in the hot-rod part of the phantom, and the defect contrast ratio in a cardiac phantom were examined. Results: For 18F-FDG in the step-and-shoot mode, nearly a 9% difference was observed in the count of projection data between the start and end positions of acquisition in the uniform part of the phantom. Based on the findings, the detectability of 12 mm hot rods was relatively poor. In the continuous acquisition mode, the count difference was corrected, and detectability of the hot rods was improved. The crosstalk from 18F to the 99mTc energy window was approximately 13%. In the cardiac phantom, the defect contrast in 99mTc images from simultaneous dual-radionuclide acquisition was improved by approximately 9% after DEW correction; the contrast after correction was similar to acquisition with 99mTc alone. Conclusion: Based on the findings, the continuous mode is useful for 18F-FDG acquisition, and DEW crosstalk correction is necessary for 99mTc-tetrofosmin imaging. [ABSTRACT FROM AUTHOR]

The occurrence of metastasis, an important breast cancer prognostic factor, depends on cell migration/invasion mechanisms, which can be controlled by regulatory and effector molecules such as Rho-associated kinase protein (ROCK-1). Increased expression of this protein promotes tumor growth and metastasis, which can be restricted by ROCK-1 inhibitors. Melatonin has shown oncostatic, antimetastatic, and anti-angiogenic effects and can modulate ROCK-1 expression. Metastatic and nonmetastatic breast cancer cell lines were treated with melatonin as well as with specific ROCK-1 inhibitor (Y27632). Cell viability, cell migration/invasion, and ROCK-1 gene expression and protein expression were determined in vitro. In vivo lung metastasis study was performed using female athymic nude mice treated with either melatonin or Y27832 for 2 and 5 wk. The metastases were evaluated by X-ray computed tomography and single photon emission computed tomography (SPECT) and by immunohistochemistry for ROCK-1 and cytokeratin proteins. Melatonin and Y27632 treatments reduced cell viability and invasion/migration of both cell lines and decreased ROCK-1 gene expression in metastatic cells and protein expression in nonmetastatic cell line. The numbers of 'hot' spots (lung metastasis) identified by SPECT images were significantly lower in treated groups. ROCK-1 protein expression also was decreased in metastatic foci of treated groups. Melatonin has shown to be effective in controlling metastatic breast cancer in vitro and in vivo, not only via inhibition of the proliferation of tumor cells but also through direct antagonism of metastatic mechanism of cells rendered by ROCK-1 inhibition. When Y27632 was used, the effects were similar to those found with melatonin treatment. [ABSTRACT FROM AUTHOR]

Objective: Assessment of the grade and type of glioma is of paramount importance for prognosis. Tumour proliferative potentials may provide additional information on the behaviour of the tumour, its response to treatment and prognosis. The purpose of this study was to investigate the correlation between diffusion tensor imaging (DTI), dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) and 99mTc-Tetrofosmin brain single-photon emission computed tomography (SPECT), and the tumour grade and Ki-67 labelling index in newly diagnosed gliomas. Methods: Study was made of patients with suspected glioma on brain MRI between December 2010 and January 2012, by DTI, DSC MRI and 99mTc-Tetrofosmin brain SPECT. The proliferative activity of each tumour was measured by deriving the Ki-67 proliferation index from immunohistochemical staining of tumour specimens. Results: Glioma was newly diagnosed in 25 patients (17 men, 8 women, aged 19-79 years, median 55 years). The Ki-67 index ranged from 1% to 80% (mean 19.4%). On evaluation of the relationship between the 99mTc-Tetrofosmin tumour uptake by gliomas was found to be significantly correlated with cellular proliferation (rho = 0.924, p < 0.0001). Regarding DTI, significant negative correlation was demonstrated between the apparent diffusion coefficient (ADC) ratio and the Ki-67 index (rho = -0.545, p = 0.0087). Significant correlation was also observed between the fractional anisotropy (FA) ratio and the Ki-67 index (rho = 0.489, p = 0.02). Strong correlation was found between relative cerebral blood volume (rCBV) and Ki-67 index (rho = 0.853, p < 0.0001), and between the 99mTc-Tetrofosmin lesion-to-normal (L/N) uptake ratio and rCBV (rho = 0.808, p ≤ 0.0001). Significant negative correlation was demonstrated between the 99mTc-Tetrofosmin L/N ratio and ADC ratio (rho = -0.513, p = 0.014). These imaging techniques were able to distinguish between low-grade and high-grade gliomas. Conclusions: Findings on DSC MRI and brain SPECT with 99mTc-Tetrofosmin metrics were more closely correlated with glioma cellular proliferation. [ABSTRACT FROM AUTHOR]

Brain MRI is the gold standard for diagnosis of brain tumors. In some cases preoperative MRI cannot predict the grade of malignancy, diagnostic information that could be very helpful to the surgeon. In such cases functional imaging with nuclear medicine techniques may prove quite useful. We present a case of a 58-year-old man with a brain tumor in the parieto-occipital region. Anatomic brain imaging by magnetic resonance imaging was indicative of a low grade astrocytoma. This was followed by planar imaging and single-photon emission computed tomography (SPECT) with 99mTctetrofosmin which showed increased radiotracer accumulation in the lesion, suggesting a glioblastoma which was histologically confirmed. We think that in the MRI era sometimes a 99mTc-tetrofosmin brain scan can contribute to diagnostic workup and improve the final management of the patient. [ABSTRACT FROM AUTHOR]

Abstract: Determining the radiochemical purity (RCP) of technetium-99m (99mTc) radiopharmaceuticals using the method described in the package insert is a time-consuming process, requiring particular attention in order to achieve accurate RCP results. The purpose of this study was to evaluate whether radio-ultra high performance liquid chromatography (radio-UHPLC) may be an alternative method for RCP testing of 99mTc-tetrofosmin, 99mTc-MAG3 and 99mTc-sestamibi. Results obtained using radio-UHPLC were in excellent agreement with the standard method, with total analysis time being reduced to less than 3min. [Copyright &y& Elsevier]

Abstract: Background: As an initial management strategy for stable ischemic heart disease (IHD), coronary revascularization therapy is thought to be equal to optimal medical therapy alone regarding prognosis. Methods: Whether or not the effects of revascularization on the prognosis of patients with stable IHD are associated with the amount of ischemic myocardium detected by nuclear stress imaging was evaluated. This retrospective study analyzed data from 4629 patients with suspected or known IHD who underwent gated stress myocardial-perfusion SPECT at 117 hospitals in Japan. The follow-up periods were three years and the combined endpoints consisted of cardiac death, nonfatal myocardial infarction, and congestive heart failure requiring hospitalization. After matching propensity scores between patients who underwent early revascularization and those who did not (n=316 per group), we compared cardiac event rates in relation to the amount of ischemic myocardium. Results: Cardiac event rates did not significantly differ between patients who underwent early revascularization and those who did not (5.4% vs. 6.4%). Among patients with≤5%, 6–10%, and >10% ischemic myocardium, cardiac event rates were 8%, 3% and 0% respectively, who underwent early revascularization compared with 4.5%, 6.1%, and 12.3%, respectively, among those who did not. Cardiac event rates were significantly lower among patients with >10% ischemic myocardium who underwent early revascularization compared with those who did not (0% vs. 12.3%, p =0.0062). Conclusions: Coronary revascularization for stable IHD does not decrease major cardiac events in all patients but might do in patients with moderate to severe ischemia. [Copyright &y& Elsevier]

Purpose: Multidrug resistance (MDR) remains a major obstacle to successful chemotherapeutic treatment of cancer. Several chemotherapeutic and radiopharmaceutical agents are substrates of the pumps encoded by the MDR genes, and therefore, their accumulation is prevented. We evaluated in vivo whether [(99m)Tc]tetrofosmin ((99m)Tc-TF) uptake is influenced by the MDR profile of gliomas.Procedures: Eighteen patients with histologically confirmed glioma were included in the study. Brain single-photon emission computed tomography by (99m)Tc-TF was performed within a week prior to surgical excision, and the expression of MRP5 was assessed by immunohistochemistry. Radiotracer accumulation was assessed by a semiquantitative method, calculating the lesion-to-normal uptake ratio.Results: Using Spearman's ρ analysis, we found no correlation between tracer uptake expressed as lesion-to-normal and MRP5 expression. There was a significant correlation between glioma aggressiveness as assessed by Ki-67/MIB-1 and MRP5 expression.Conclusion: The present data suggest that (99m)Tc-TF uptake is not influenced by glioma's MDR phenotype. Thus, (99m)Tc-TF constitutes a suitable radiotracer for imaging gliomas. [ABSTRACT FROM AUTHOR]

Diabetic patients have a high risk for cardiovascular events. The role of myocardial perfusion imaging was investigated in asymptomatic diabetic patients to evaluate short-term prognosis in a Japanese population. A total of 506 asymptomatic patients ≥50 years of age who had carotid artery maximum intima-media thickness ≥1.1 mm, urinary albumin excretion of ≥30 mg/g creatinine, with additional criteria of abdominal obesity, low HDL cholesterol, high triglyceride level, and hypertension were enrolled and followed up over a 3-year period. Gated SPECT with stress-rest protocol was performed and analyzed by summed defect scores and QGS software. One-year cardiovascular events were analyzed. Myocardial ischemia was observed in 17% of patients, and abnormal perfusion findings of ischemia and/or scar were observed in 32% of patients. By the end of the 1-year follow-up, 33 (6.5%) cardiovascular events occurred including 6 all-cause deaths. Patients with summed stress score (SSS) >8 had a higher incidence of either death or cardiovascular events. Event-free survival rates for SSS 0–3, 4–8, 9–13, and ≥14 were 0.96, 0.95, 0.82, and 0.76, respectively. Multivariate Cox regression analysis showed that significant variables were SSS, history of cerebrovascular accident, and electrocardiographic abnormality at rest. The 1-year interim summary showed that cardiovascular events were significantly higher in patients with SPECT abnormality, although hard cardiac event rate was relatively low. Targeted treatment strategy is required for asymptomatic but potentially high-risk diabetic patients. [ABSTRACT FROM AUTHOR]

A new formulation of a freeze-dried kit for the labeling of tetrofosmin with technetium-99m has been developed. The kit contains lyophilized mixture of 0.320 mg tetrofosmin [6,9-bis(2-ethoxyethyl)-3,12-dioxa-6,9-diphosphatetradecane], 0.025 mg stannous chloride dihydrate, 5 mg sodium tartrate and 5 mg sodium hydrogen carbonate. The product contains no antimicrobial preservative. When 99mTc pertechnetate up to 6 mL saline containing 200 mCi is added to lyophilized mixture, a lipophilic, cationic 99mTc complex is formed, 99mTc-tetrofosmin. The performance of newly developed kit is compared with commercially available MYOVIEW kit for heart imaging. The patient studies show that the images of heart obtained by 99mTc-tetrofosmin prepared by new formulation are equally good to MYOVIEW. [ABSTRACT FROM AUTHOR]

Background: The impact of myocardial perfusion imaging (MPI) on prediction of risk for future cardiac events was examined by comparing predictions based on clinical information alone and in combination with MPI findings. Methods and Results: A 3-cardiologist Cardiac Event Prediction Panel (CEPP) estimated three-year cardiac event (non-fatal MI; aborted sudden cardiac death; cardiac death) risk based on clinical data (C) for 371 subjects. CEPP repeated this estimation after receiving Summed Stress Scores (SSS) and Summed Rest Scores (SRS) from blinded reading of rest-stress Tc-tetrofosmin MPI SPECT studies (C + MPI). The C and C + MPI estimates were then compared with three-year and total event rates. MPI was normal (SSS ≤ 3) in 227 patients (61%), mildly abnormal (SSS 4-8) in 31 (8%), moderately abnormal (SSS 9-13) in 36 (10%), and severely abnormal (SSS > 13) in 77 (21%). Eighteen cardiac events occurred within 3 years and 33 occurred during a mean follow-up of 3.9 years. C + MPI estimates of low risk (<1-1.5%/year) identified significantly more patients who did not have events than C. C + MPI three-year event-rate predictions were more accurate than those made with C ( P < .01). C + MPI categorization also provided better delineation of incremental risk on time-to-event analyses. Conclusions: Tc-tetrofosmin MPI single photon emission computed tomography (SPECT) findings significantly improve accuracy of cardiac event rate prediction compared to those based on clinical information alone. [ABSTRACT FROM AUTHOR]

Percutaneous transluminal coronary angioplasty is a well-established therapeutic method in selected patients with coronary artery disease. The aim of this study was to assess the incremental prognostic value of technetium-99m (99mTc)-tetrofosmin myocardial gated-single- photon emission computed tomography (SPECT) in asymptomatic patients after coronary artery stenting. A total of 246 consecutive patients (aged 55.5 ± 8.2 years, 182 men) participated in the study with a median follow-up of 9.5 years (interquartile ra 5.8–10.5 years). All patients underwent exercise gated-SPECT myocardial imaging within 5–7 months. Myocardial scintigrams were performed using 99mTctetrofosmin, and were evaluated calculating the summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) indexes. Cardiovascular death and non-fatal myocardial infarction were considered as hard cardiac events, and late revascularization (>3 months after myocardial SPECT) procedures as soft events. Receiver-operating characteristic (ROC) analysis was used to test the prognostic ability of SSS and SDS for cardiac events. Cox proportional hazards models were used to evaluate the incremental value of SPECT variables. Cardiac death occurred in 12 (4.9%) patients and non-fatal myocardial infarction in 20 (8.1%) patients. In addition, 60 (24.4%) patients underwent a late revascularization procedure. Using ROC analysis the optimal cut-offs of SSS (AUC = 0.94; 95% CI 0.92–0.97) and SDS (AUC = 0. 76; 95% CI 0.70–0.82) for the prediction of cardiac events were 10 and 1.7, respectively. Multiple Cox regression analyses revealed that SSS > 10 (HR = 24.2; 95% CI 7.44–78.79) and SDS > 1.7 (HR = 2.72; 95% CI 1.23–6.00) provided incremental prognostic value over clinical and exercise test data for the composite end points of any cardiac event. 99mTc-tetrofosmin myocardial gated- SPECT, performed 6 months post-percutaneous coronary intervention (PCI), provides incremental prognostic information for the prediction of cardiac events in asymptomatic patients after PCI. [ABSTRACT FROM AUTHOR]

In order to investigate the clinical significance of 99mTc-Tetrofosmin (TF) scintigraphy in the evaluation of lung cancer and mediastinal lymphoid node involvement, 33 patients with pulmonary neoplasmas were subjected to both 99mTc-TF scintigraphies and CT scans in one week before their operations or puncturations. All the images were judged visually and the emission images were analyzed with semi-quantitative methods in addition. The results of each group were compared. There was marked difference in target/non-target (T/N) ratio between the lung cancer group and the benign lesion group ( P<0.001). Moreover, in the lung cancer group, T/N ratio in tomographies was significantly higher than that in planar images ( P<0.01). The sensitivity and accuracy of semi-quantitative analysis in 99mTc-TF SPECT were significantly higher than those of CT in the diagnosis of pulmonary neoplasmas ( P<0.05 and P<0.01 respectively), so was the sensitivity of 99mTc-TF SPECT vs CT in the diagnosis of mediastinal lymphoid node metastasis ( P<0.05). It was also found that epidermoid squamous cell carcinomas and adenocarcinomas had a higher T/N ratio than in small cell carcinomas ( P<0.05), and 2 h washout rate (WR) of adenocarcinomas was higher than that of epidermoid squamous cell carcinomas ( P<0.05). In conclusion, 99mTc-TF scintigraphy showed a favorable diagnostic accuracy in appraising lung cancers and mediastinal lymph node metastases. Furthermore semi-quantitative technology can improve the accuracy, and is potential to offer some information about histological type of the cancer tissue. Therefore, 99mTc-TF scintigraphy will be a useful tool in the diagnosis and staging of lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Although meningiomas usually have a benign clinical course, atypical and malignant types of this brain tumor are associated with high recurrence rates and poor outcome; thus, DNA ploidy and S-phase – as determined by DNA flow cytometry – are useful indicators of their biological behavior. Brain single-photon emission computed tomography (SPECT) has been suggested as a potentially useful modality for the metabolic assessment of various brain tumors. This study evaluated whether 99mTc-Tetrofosmin (99mTc-TF) uptake correlates with meningioma proliferative activity, as assessed by flow cytometry analysis. Patients and methods: Ten consecutive patients (3 males, 7 females, mean age 64.6 years) with a diagnosis of a symptomatic intracranial meningioma, planned to undergo surgery, were studied. Brain SPECT by 99mTc-TF was performed within a week prior to surgical excision and flow cytometric analysis was performed in the excised tissue. Tumoral radiotracer accumulation was first assessed visually. Semiquantitative image analysis was also performed, by calculating the lesion-to-normal (L/N) uptake ratio. Results: Benign meningiomas were diagnosed in 8/10 cases, the remaining 2/10 patients had anaplastic lesions. DNA aneuploidy was found in 2 lesions, the remaining tumors were diploid. There was a significant correlation between tracer uptake and the percentage of the cell fraction on S-phase (r =0.733, P =0.05). There was also a positive correlation between tracer uptake and the level of aneuploidy and tumor grade. Conclusion: These results imply that 99mTc-TF brain SPECT may have the ability to discriminate benign meningiomas from malignant meningiomas pre-operatively, the tracer uptake being a likely indicator of their proliferative activity. [Copyright &y& Elsevier]

Diabetes mellitus is an independent risk factor for acute myocardial infarction. Thus, a surveillance study was conducted as part of studies to create a national database related to electrocardiogram (ECG)-gated myocardial perfusion single-photon emission computed tomography (SPECT) of ischemic heart disease. Single-photon emission computed tomography was conducted in patients with type 2 diabetes mellitus and their prognoses will be followed for 3 years, stratified by patients’ clinical background and SPECT findings. A total of 513 patients from 50 institutions were enrolled in this study, 297 of whom were men (age 66.2 ± 0.4 years, mean ± SEM) and 261 women (age 67.8 ± 0.5 years). They have a history of retinopathy (25.3%), neuropathy (19.9%), cerebrovascular disorder, chronic obstructive pulmonary disease, and photocoagulation. Major risk factors for present disease were hypertension (82.3%) and hyperlipidemia (79.7%). In 244 patients (129 men and 115 women), body mass index (BMI) was 25 or more. Fifty-two of them (10.1%) underwent coronary angiography; of these, 26 (50.0%) had no coronary artery lesions with 75% or more stenosis, and only 1 (1.9%) had a left main trunk with 50% or more stenosis. An overwhelming majority of patients (94.3%) underwent SPECT imaging by a 1-day stress-followed-by-rest procedure. Stress procedure was exercise in most (70.8%) patients, followed by dipyridamole infusion in 14.6%, adenosine infusion in 6.6%, and adenosine triphosphate infusion in 5.7%. Endpoint of stress examination was most often fatigue in lower limbs (40.7%), followed by completion of pharmacological stress protocol (28.7%), and achievement of target heart rate (26.3%). The largest number of patients (198, 38.6%) received 99mTc-tetrofosmin at an initial dosage of 200–300 MBq (mean 331 ± 3 MBq) followed by a second dosage of 700–800 MBq (mean 748 ± 8 MBq). Among them, 491 (95.7%) received some kind of therapeutic drug: hypoglycemic drugs were used by the largest number (83.2%), followed by hypotensive (66.7%), hypolipidemic (40.7%), and antiplatelet drugs (27.7%), vasodilators (5.5%), and antioxidants and others (2.3%). This study was designed to clarify the correlation between coronary artery disease and diabetes mellitus as its risk factor based on the clinical and imaging findings. Patient enrollment was closed on September 30, 2005, and follow-up is now under way. [ABSTRACT FROM AUTHOR]

Objective: Gated single-photon emission computed tomography (G-SPECT) was used to evaluate cardiac risk associated with noncardiac surgery and determine the benefits and indications of this technique for this type of surgery. Materials and Methods: Patients scheduled to undergo noncardiac surgery under the supervision of anesthesiologists and subjected to preoperative cardiac evaluation using G-SPECT during the 26-month period between June 2000 and August 2002 were followed for the presence/absence of cardiac events (i.e., cardiac death, myocardial infarction, unstable angina, congestive heart failure, or fatal arrhythmia) during surgery and the postoperative period until discharged. Relationships between the occurrence of cardiac events and preoperative G-SPECT findings were evaluated. Results: A total of 39 patients underwent G-SPECT; 6 of the 39 exhibited abnormal ejection fraction (left ventricular ejection fraction, LVEFor=50 ml). Surgery was suspended for three of these six patients and cardiac events developed in the remaining three patients. Both abnormal perfusion images (PI) and abnormal wall thickening (WT) were observed in all six patients. All six patients exhibited abnormal LVEF and/or ESV. Three patients had either abnormal PI or WT, and a cardiac event occurred in one of them. Of the five patients who experienced cardiac events during or after surgery, two exhibited a short run of ventricular tachycardia requiring a continuous administering of antiarrhythmic drugs, whereas the remaining three patients exhibited cardiac failure requiring inotropic support following surgery. Conclusions: The results of this study indicate that the occurrence of perioperative cardiac events can be predicted by considering the severity of expected surgical stress and preoperative G-SPECT findings for LVEF, PI, and WT. We conclude that G-SPECT is quite useful for cardiac risk assessment in patients undergoing noncardiac surgery. [ABSTRACT FROM AUTHOR]

This study examined the suitability of a nuclear imaging technique using 99mTc-tetrofosmin as an agent to assess the heart functions of healthy micropigs. The mean age of the pigs was 360 days (male), and the mean body weight was 35.3 kg ranging from 34.5-36 kg. There were no significant perfusion defects in any of the reconstructed images. Gated single-photon emission computed tomography imaging can be used to calculate the ventricular volume and ejection fraction (EF). In this case, an EF of 79% was calculated from the ventricular volume of the end-systolic image (10 ml) subtracted from that of the end-diastolic volume (49 ml). A perfusion defect (particularly the apex, lateral wall) is unlikely because of the presence of a preserved wall motion in a segment with a defect. It is concluded that quantitative cardiac scintigraphy, using 99mTc-tetrofosmin is an adequate technique for estimating the heart functions of healthy micropigs. [ABSTRACT FROM AUTHOR]

Objective: The differentiation between brain tumor recurrence and post-irradiation injury remains an imaging challenge. Computed tomography (CT) and magnetic resonance imaging (MRI) cannot always distinguish between the two. Although glioma cell line studies substantiated a plausible imaging superiority of (99m)Tc-tetrofosmin ((99m)Tc-TF) over other radiopharmaceuticals, little has been reported on its in vivo imaging properties. We assessed (99m)Tc-TF single-photon emission CT (SPECT) in cases where morphologic brain imaging was inconclusive between recurrence and radionecrosis. Methods: A total of 11 patients (7 men, 4 women) were evaluated. The initial diagnosis was glioblastoma multiforme (4), anaplastic astrocytoma (1), anaplastic oligodendroglioma (3), grade-II astrocytoma (2), and low-grade oligodendroglioma (1). All patients had been operated on and then received adjuvant external-beam radiotherapy. After a mean follow-up period of 25 months, there was clinical suspicion of recurrence, for which (99m)Tc-TF SPECT was performed. Results: In 8/11 cases, an abnormally increased tracer uptake appeared in the region that CT and/or MRI indicated as suspicious; in half of these cases, recurrence was confirmed histologically after surgery and in the other four by growth of the lesion over a 6-month follow-up period, and clinical deterioration. The remaining 3/11 patients had faint tracer uptake in the suspicious region, compatible with radiation injury; these lesions remained morphologically unaltered in a mean 12-month follow-up period, with no clinical deterioration in the patient's condition, a course strongly favoring the diagnosis of radiation injury. Conclusions: Metabolic brain imaging by (99m)Tc-TF could offer useful information in the workup of treated brain tumors, where radiomorphologic findings between recurrence and radionecrosis are inconclusive. [ABSTRACT FROM AUTHOR]

201Thallium (TL), 99mTc-tetrofosmin (TF), and 99mTc-sestamibi (MIBI) are extensively used as myocardial perfusion agents. The objective of the present study was to evaluate their kinetics under acute ischemia–reperfusion. Isolated rat hearts, perfused by the Langendorff method at a constant flow rate of 10 ml/min, were allotted to normal control, mild ischemia, and severe ischemia groups, in which 20-min tracer wash-in was conducted followed by a 25-min tracer washout. No-flow ischemia (15 min for mild ischemia groups; 30 min for severe ischemia groups) was induced before conducting wash-in and washout in the ischemia groups. Whole-heart radioactivity was determined with an external gamma detector. Myocardial flow rate ( K 1, ml/min) and clearance rate ( k 2, min−1) were calculated. K 1TL, K 1TF, and K 1MIBI decreased according to the severity of ischemia ( K 1TL 5.32 ± 0.53, 4.76 ± 0.70, and 1.44 ± 0.59; K 1TF 3.80 ± 0.70, 2.73 ± 0.99, and 1.09 ± 0.45; and K 1MIBI 3.45 ± 1.10, 2.15 ± 0.82, and 1.05 ± 0.13, in the normal control, mild, and severe ischemia groups, respectively). K 1 was significantly higher for TL than for the 99mTc tracers ( P < 0.05), but the 99mTc tracers had equivalent K 1 values. k 2TL increased significantly ( P < 0.05) in the ischemia groups ( k 2TL 0.062 ± 0.013, 0.11 ± 0.045, and 0.12 ± 0.035), but showed no significant difference between the ischemia groups. k 2MIBI and k 2TF were significantly ( P < 0.05) lower than k 2TL and increased significantly ( P < 0.05) in the severe ischemia group ( k 2TF 0.0056 ± 0.0022, 0.0037 ± 0.0015, and 0.024 ± 0.015; and k 2MIBI 0.00072 ± 0.0011, 0.00038 ± 0.00076, and 0.042 ± 0.034). k 2MIBI was significantly ( P < 0.05) lower than k 2TF in the normal control and mild ischemia groups. Tracer extraction was higher for TL than for the 99mTc tracers and all tracers decreased according to the severity of ischemia–reperfusion in the three tracer groups. The clearance kinetics of not only MIBI but also TF is possibly useful for the evaluation of the severity of ischemia, and the Langendorff method and a methodological approach by continuous determinations of radioactivity may serve for the quantitative analysis of tracer kinetic profiles. [ABSTRACT FROM AUTHOR]