technetium-tc-99m-tetrofosmin and Disease-Models--Animal

The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αvβ3. We developed a Tc-99m and TAMRA labeled peptide, Tc-99m SDV-ECG-K-TAMRA for multimodal imaging of angiogenesis. Tc-99m SDV-ECG-K-TAMRA was prepared in high yield (>96%) and showed low cytotoxicity. Tc-99m tetrofosmin images 1 week after operation, revealed significantly decreased perfusion of the ischemic hindlimb, and the perfusion recovered gradually for 4 weeks. In contrast, Tc-99m SDV-ECG-K-TAMRA uptake was maximal 1 week after the operation (ischemic-to-non-ischemic uptake ratio =5.03±1.01) and decreased gradually. The ischemic-to-non-ischemic ratio of Tc-99m SDV-ECG-K-TAMRA and Tc-99m tetrofosmin was strongly negatively correlated (r =-0.94). A postmortem analysis revealed increased angiogenesis markers and uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Our in vivo and in vitro studies revealed substantial uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Tc-99m SDV-ECG-K-TAMRA could be a good candidate dual-modality imaging agent to assess angiogenesis.

Topics: Animals; Disease Models, Animal; Fluorescent Dyes; Hindlimb; Ischemia; Mice; Microscopy, Confocal; Multimodal Imaging; Neovascularization, Physiologic; Oligopeptides; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Rhodamines; Technetium; Tissue Distribution

Data on the in vivo myocardial kinetics of (123)I-metaiodobenzylguanidine ((123)I-MIBG) are scarce and have always been obtained using planar acquisitions. To clarify the normal kinetics of (123)I-MIBG in vivo over time, we designed an experimental protocol using a 3-dimensional (3D) dynamic approach with a cadmium zinc telluride (CZT) camera.. We studied 6 anesthetized pigs (mean body weight, 37 ± 4 kg). Left ventricular myocardial perfusion and sympathetic innervation were assessed using (99m)Tc-tetrofosmin (26 ± 6 MBq), (123)I-MIBG (54 ± 14 MBq), and a CZT camera. A normal perfusion/function match on gated SPECT was the inclusion criterion. A dynamic acquisition in list mode started simultaneously with the bolus injection of (123)I-MIBG, and data were collected every 5 min for the first 20 min and then at acquisition steps of 30, 60, 90, and 120 min. Each step was reconstructed using dedicate software and reframed (60 s/frame). On the reconstructed transaxial slice that best showed the left ventricular cavity, regions of interest were drawn to obtain myocardial and blood pool activities. Myocardial time-activity curves were generated by interpolating data between contiguous acquisition steps, corrected for radiotracer decay and injected dose, and fitted to a bicompartmental model. Time to myocardial maximum signal intensity (MSI), MSI value, radiotracer retention index (RI, myocardial activity/blood pool integral), and washout rate were calculated. The mediastinal signal was measured and fitted to a linear model.. The myocardial MSI of (123)I-MIBG was reached within 5.57 ± 4.23 min (range, 2-12 min). The mean MSI was 0.426% ± 0.092%. Myocardial RI decreased over time and reached point zero at 176 ± 31 min (range, 140-229 min). The ratio between myocardial and mediastinal signal at 15 and 125 min and extrapolated at 176 and 4 h was 5.45% ± 0.61%, 4.33% ± 1.23% (not statistically significant vs. 15 min), 3.95% ± 1.46% (P < 0.03 vs. 125 min), and 3.63% ± 1.64% (P < 0.03 vs. 176 min), respectively. Mean global washout rate at 125 min was 15% ± 14% (range, 0%-34%), and extrapolated data at 176 min and 4 h were 18% ± 18% (range, 0.49%-45%) and 25% ± 23% (range, 1.7%-56.2%; not statistically significant vs. 176 min), respectively.. 3D dynamic analysis of (123)I-MIBG suggests that myocardial peak uptake is reached more quickly than previously described. Myocardial RI decreases over time and, on average, is null about 3 h after injection. The combination of an early peak and variations in delayed myocardial uptake could result in a wide physiologic range of washout rates. Mediastinal activity appears to be constant over time and significantly lower than previously described in planar studies, resulting in a higher heart-to-mediastinum ratio.

Topics: 3-Iodobenzylguanidine; Animals; Cadmium; Disease Models, Animal; Heart; Heart Ventricles; Imaging, Three-Dimensional; Iodine Radioisotopes; Models, Statistical; Myocardium; Organophosphorus Compounds; Organotechnetium Compounds; Oxygen Consumption; Perfusion; Radiopharmaceuticals; Swine; Sympathetic Nervous System; Tellurium; Time Factors; Tomography, Emission-Computed, Single-Photon; Zinc

To develop a mouse model of cardiac injury after partial heart irradiation (PHI) and to test whether dual energy (DE)-microCT and 4-dimensional (4D)-microCT can be used to assess cardiac injury after PHI to complement myocardial perfusion imaging using micro-single photon emission computed tomography (SPECT).. To study cardiac injury from tangent field irradiation in mice, we used a small-field biological irradiator to deliver a single dose of 12 Gy x-rays to approximately one-third of the left ventricle (LV) of Tie2Cre; p53(FL/+) and Tie2Cre; p53(FL/-) mice, where 1 or both alleles of p53 are deleted in endothelial cells. Four and 8 weeks after irradiation, mice were injected with gold and iodinated nanoparticle-based contrast agents, and imaged with DE-microCT and 4D-microCT to evaluate myocardial vascular permeability and cardiac function, respectively. Additionally, the same mice were imaged with microSPECT to assess myocardial perfusion.. After PHI with tangent fields, DE-microCT scans showed a time-dependent increase in accumulation of gold nanoparticles (AuNp) in the myocardium of Tie2Cre; p53(FL/-) mice. In Tie2Cre; p53(FL/-) mice, extravasation of AuNp was observed within the irradiated LV, whereas in the myocardium of Tie2Cre; p53(FL/+) mice, AuNp were restricted to blood vessels. In addition, data from DE-microCT and microSPECT showed a linear correlation (R(2) = 0.97) between the fraction of the LV that accumulated AuNp and the fraction of LV with a perfusion defect. Furthermore, 4D-microCT scans demonstrated that PHI caused a markedly decreased ejection fraction, and higher end-diastolic and end-systolic volumes, to develop in Tie2Cre; p53(FL/-) mice, which were associated with compensatory cardiac hypertrophy of the heart that was not irradiated.. Our results show that DE-microCT and 4D-microCT with nanoparticle-based contrast agents are novel imaging approaches complementary to microSPECT for noninvasive assessment of the change in myocardial vascular permeability and cardiac function of mice in whom myocardial injury develops after PHI.

Topics: Animals; Capillary Permeability; Contrast Media; Coronary Vessels; Disease Models, Animal; Four-Dimensional Computed Tomography; Gold; Heart; Heart Ventricles; Mice; Nanoparticles; Organophosphorus Compounds; Organotechnetium Compounds; Radiation Injuries, Experimental; Tomography, Emission-Computed, Single-Photon; X-Ray Microtomography

Absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) provide incremental diagnostic and prognostic information over relative perfusion alone. Recent development of dedicated cardiac SPECT cameras with better sensitivity and temporal resolution make dynamic SPECT imaging more practical. In this study, we evaluate the measurement of MBF using a multipinhole dedicated cardiac SPECT camera in a pig model of rest and transient occlusion at stress using 3 common tracers: (201)Tl, (99m)Tc-tetrofosmin, and (99m)Tc-sestamibi.. Animals (n = 19) were injected at rest/stress with (99m)Tc radiotracers (370/1,100 MBq) or (201)Tl (37/110 MBq) with a 1-h delay between rest and dipyridamole stress. With each tracer, microspheres were injected simultaneously as the gold standard measurement for MBF. Dynamic images were obtained for 11 min starting with each injection. Residual resting activity was subtracted from stress data and images reconstructed with CT-based attenuation correction and energy window-based scatter correction. Dynamic images were processed with kinetic analysis software using a 1-tissue-compartment model to obtain the uptake rate constant K(1) as a function of microsphere MBF.. Measured extraction fractions agree with those obtained previously using ex vivo techniques. Converting K(1) back to MBF using the measured extraction fractions produced accurate values and good correlations with microsphere MBF: r = 0.75-0.90 (P < 0.01 for all). The correlation in the MFR was between r = 0.57 and 0.94 (P < 0.01).. Noninvasive measurement of absolute MBF with stationary dedicated cardiac SPECT is feasible using common perfusion tracers.

Topics: Animals; Blood Flow Velocity; Coronary Occlusion; Coronary Vessels; Disease Models, Animal; Humans; Image Processing, Computer-Assisted; Kinetics; Models, Statistical; Myocardium; Organophosphorus Compounds; Organotechnetium Compounds; Swine; Technetium Tc 99m Sestamibi; Thallium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Left ventricular function is altered during and after AMI. Regional function can be determined by cardiac magnetic resonance (CMR) wall thickening, and velocity encoded (VE) strain analysis. The aims of this study were to investigate how regional myocardial wall function, assessed by CMR VE-strain and regional wall thickening, changes after acute myocardial infarction, and to determine if we could differentiate between ischemic, adjacent and remote segments of the left ventricle.. Ten pigs underwent baseline CMR study for assessment of wall thickening and VE-strain. Ischemia was then induced for 40-minutes by intracoronary balloon inflation in the left anterior descending coronary artery. During occlusion, (99m)Tc tetrofosmin was administered intravenously and myocardial perfusion SPECT (MPS) was performed for determination of the ischemic area, followed by a second CMR study. Based on ischemia seen on MPS, the 17 AHA segments of the left ventricle was divided into 3 different categories (ischemic, adjacent and remote). Regional wall function measured by wall thickening and VE-strain analysis was determined before and after ischemia.. Mean wall thickening decreased significantly in the ischemic (from 2.7 mm to 0.65 mm, p < 0.001) and adjacent segments (from 2.4 to 1.5 mm p < 0.001). In remote segments, wall thickening increased significantly (from 2.4 mm to 2.8 mm, p < 0.01). In ischemic and adjacent segments, both radial and longitudinal strain was significantly decreased after ischemia (p < 0.001). In remote segments there was a significant increase in radial strain (p = 0.002) while there was no difference in longitudinal strain (p = 0.69). ROC analysis was performed to determine thresholds distinguishing between the different regions. Sensitivity for determining ischemic segments ranged from 70-80%, and specificity from 72%-77%. There was a 9% increase in left ventricular mass after ischemia.. Differentiation thresholds for wall thickening and VE-strain could be established to distinguish between ischemic, adjacent and remote segments but will, have limited applicability due to low sensitivity and specificity. There is a slight increase in radial strain in remote segments after ischemia. Edema was present mainly in the ischemic region but also in the combined adjacent and remote segments.

Topics: Animals; Biomechanical Phenomena; Disease Models, Animal; Edema, Cardiac; Heart Ventricles; Magnetic Resonance Imaging; Myocardial Contraction; Myocardial Infarction; Myocardial Perfusion Imaging; Organophosphorus Compounds; Organotechnetium Compounds; Predictive Value of Tests; Radiopharmaceuticals; Sus scrofa; Time Factors; Tomography, Emission-Computed, Single-Photon; Ventricular Function, Left

Myocardial perfusion single-photon emission computed tomography (MPS) can be used to assess myocardium at risk in occlusive coronary ischaemia. The aim was to develop a method to quantify myocardium at risk as perfusion defect size on ex vivo MPS using co-registration and fusion with ex vivo magnetic resonance imaging (MRI).. Pigs (n = 19) were injected 99mTc-tetrofosmin prior to concluding 40 min of coronary artery occlusion, followed by reperfusion and MRI contrast injection. The excised heart was imaged with T1-weighted MRI and MPS, and images were co-registered using freely available software (Segment v1.8, http://segment.heiberg.se). The left ventricle was semi-automatically delineated in MRI and copied to MPS. The threshold for a MPS perfusion defect was defined as the mean counts in the MPS image at the MRI-determined border between remote myocardium and air. The threshold was measured using count maxima set to the 100th-95th percentile of counts within the myocardium. The count maximum that gave the lowest threshold variability (SD) was considered the most robust.. A count maximum using the 100th percentile yielded a threshold of (mean ± SD) 55 ± 6·2%. This method showed the lowest SD compared to 99th-95th percentile count maxima (6·6-7·2%).. We describe a method for objective quantification of myocardium at risk as perfusion defect size on MPS using knowledge of the anatomy of the myocardium from co-registered MRI. This enables simultaneous quantification of myocardium at risk by MPS and infarct size by MRI for the evaluation of treatments for myocardial infarction.

Topics: Animals; Contrast Media; Coronary Circulation; Coronary Occlusion; Disease Models, Animal; Female; Magnetic Resonance Imaging; Male; Myocardial Infarction; Myocardium; Organophosphorus Compounds; Organotechnetium Compounds; Predictive Value of Tests; Radiopharmaceuticals; Swine; Tomography, Emission-Computed, Single-Photon

Breast cancer is the leading cause of death among women, and morphine is used to relieve the pain of patients with cancer. The data on the effects of morphine on tumour growth and angiogenesis are contradictory. We determined in mouse breast cancer model whether analgesic doses of morphine would affect tumour angiogenesis, and then the correlation between microvessel density (MVD), Doppler sonography (DS) and 99mTc-Tetrofosmin (TF) uptake. Ehrlich ascites tumour cell xenografts, Pgp-negative tumour were divided into two groups: (a) Morphine sulphate [0.714 mg/kg/day (equivalent to 50 mg per day for a 70 kg human)], (b) no-morphine. For the determination of angiogenesis in mice tumour tissue, TF scintigraphy, microvessel density and DS were done. MVD was significantly different between groups (49.4±1.8 vs. 41.8±1.9, morphine and no-morphine groups, respectively, P<0.001). A strong correlation was found between late uptakes of mass at scintigraphy and degree of angiogenesis in histopathologic examination (r=0.52, P<0.01). There was statistically significant inverse correlation between degree of angiogenesis in histopathologic examination and washout ratio of TF (r=0.40, P<0.05). The higher values for angiogenesis are related to higher TF reuptake. There was no statistically significant correlation between DS and TF. A strong correlation was found between MVD and grade of DS (r=0.51, P<0.01). Our preclinical mice study indicates that morphine at clinically relevant doses stimulates angiogenesis, and angiogenesis triggered of morphine is demonstrated with MVD and DS, but not TF. However, uptake and washout of TF are compared with immunohistochemically assessed morphine-stimulated angiogenesis in tumour tissue.

Topics: Animals; Breast Neoplasms; Carcinoma, Ehrlich Tumor; Disease Models, Animal; Female; Immunohistochemistry; Mice; Mice, Inbred BALB C; Morphine; Narcotics; Neovascularization, Pathologic; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Ultrasonography, Doppler

Enhanced washout of 99mTc-tetrofosmin (TF) has been reported in patients with hypertrophic cardiomyopathy (HCM). Here, using quantitative dual-autoradiography, the relationship between TF retention abnormality and metabolism depicted by 125I-BMIPP uptake was investigated quantitatively in a hamster model of cardiomyopathy.. Early and delayed TF images were obtained at 5 min (7 cardiomyopathic and 5 normal hamsters) and 60 min (8 cardiomyopathic and 5 normal hamsters) after injection, respectively. BMIPP image was obtained 5 min after injection. Five cardiomyopathic and 5 normal hamsters were evaluated histologically. Percent uptake of TF and BMIPP in the heart was measured by an auto-well counter. The left ventricular wall was divided into 12 segments, and the relative regional uptake of TF and BMIPP was measured for each segment. Heterogeneity of radioactive distribution was determined by the standard deviation (SD) of radioactive counts in the left ventricular wall on autoradiogram. The uptake of early TF, delayed TF, and BMIPP in cardiomyopathic hamsters was 8.8%, 20.3%, and 25.3% lower than that in normal hamsters, p < 0.05, p < 0.01, and p < 0.001, respectively. In normal hamsters, distribution of radioactivity in all images was homogeneous, and the SD values were about 13. In cardiomyopathic hamsters, heterogeneous distribution was observed on all images, and the degree of heterogeneity was marked on delayed TF and BMIPP images. The SD was 19.7 +/- 1.2 for early TF image, 25.5 +/- 1.4 for delayed TF image, and 31.7 +/- 2.4 for BMIPP image, respectively. A weak linear correlation was observed between the relative regional uptake of the delayed TF and BMIPP in cardiomyopathic hamsters (r = 0.57). Electron microscopy demonstrated ultra-structural changes in mitochondria of cardiomyopathic hamsters.. Degree of retention abnormality on delayed TF image corresponded to the metabolic abnormality, probably due to mitochondrial dysfunction, depicted on BMIPP imaging.

Topics: Animals; Autoradiography; Cardiomyopathies; Cricetinae; Disease Models, Animal; Fatty Acids; Heart Ventricles; Image Interpretation, Computer-Assisted; Iodine Radioisotopes; Iodobenzenes; Mesocricetus; Metabolic Clearance Rate; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Tissue Distribution