Evaluation of the visualized left atrium by 201Tl myocardial scintigraphy

201Tl myocardial scintigraphy was evaluated in patients with 18 mitral stenosis cases. Left atrium was to be seen in ANT (16.7%), LAO (16.7%), MLAO (16.7%) and L-LAT (11.1%), respectively. Furthermore, 201Tl uptake ratio of left atrium, right ventricle, pulmonary area tended significantly to increase in visible group compared with invisible group. PCW pressure was correlated with left atrial Tl uptake (r = 0.51, p less than 0.005), and it indicated some correlation between left atrial pressure and 201Tl uptake.     

Clinical comparison of 99mTc-diethylenetriaminepentaacetic acid-human serum albumin (99mTc-HSA-D) and 99mTc-human serum albumin (99mTc-HSA) for cardiac blood pool imaging

99mTc-HSA-D has been developed as a new blood pool scanning agent. Clinical comparison of 99mTc-HSA-D and 99mTc-HSA was made in 16 cases. The activity concentration of 99mTc in blood was measured during 2 hours after the injection in five cases. 99mTc-HSA-D showed higher concentration compared to 99mTc-HSA with the passage of time. Quantitative analysis of contrast between left ventricle and septum was performed on end diastolic frames of gated images 10 minutes after the injection. There was no obvious difference between 99mTc-HSA-D and 99mTc-HSA. The subjective comparison of detectability of lesions between the two agents was performed on three directional gated images. 99mTc-HSA-D was superior to 99mTc-HSA, because the images of the latter deteriorated with the passage of time. On anterior view images 1 hour after the injection, left ventricle/lung and abdominal aorta/background count ratios were greater for 99mTc-HSA-D in many cases. There was no obvious difference in liver/background and kidney/background count ratios between the two agents. Urinary excretion of 99mTc was considerably lesser for 99mTc-HSA-D. The results indicated that 99mTc-HSA-D was superior to 99mTc-HSA for cardiac blood pool imaging.     

Quality control of201TlCl solution obtained at IPEN-CNEN/SP

The radiopharmaceutical²⁰¹TlCl(thallium-201 chloride) is used in nuclear medicine for myocardial visualization. The solution of²⁰¹TlCl was prepared using²⁰¹Tl obtained by irradiating a natural mercury target with protons from the CV-28 cyclotron installed at IPEN-CNEN/SP. This solution was subjected to different quality control processes required for its use in medicine. Some of these controls concerned the determination of the radionuclidic impurities:²⁰⁰Tl,²⁰²Tl and²⁰³Hg; the chemical identification of²⁰¹Tl⁺; the hydrazine concentration, mercury contamination and the presence of phosphate. Furthermore. the biological distribution in Wistar rats and tests for sterility, pyrogenicity and toxicity were carried out. It was verified that the solution obtained was in the form of thallous chloride. This radiopharmaceutical gave good heart images in animals but due to the high levels of²⁰⁰Tl and²⁰²Tl its use in humans is not possible unless enriched²⁰²Hg is used as target in the irradiation.     

Preparation and biological evaluation of the new chlorin photosensitizer T3,4BCPC for detection and treatment of tumors

The new water-soluble photosensitizer 5,10,15,20-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl]chlorin (T3,4BCPC) has been prepared, characterized and labeled with 99mTc radionuclide. The radiotracer was evaluated for tissue distribution in Wistar rats. Accumulation of administrated activities in the liver, kidney, bladder and large intestine at 4 h post-injection indicated that the labeled ligand was largely eliminated through the renal and partly through the hepatobiliary system. In vivo biodistribution studies of the labeled compound were carried out in rodent and murine tumor models in comparison with other tumor-seeking radiopharmaceuticals such as 99mTc(V)-dimercaptosuccinic acid (DMSA), 201thallous chloride (TlCl) and 99mTc-citrate using a gamma camera computer system. In N-nitrosomethylurea (NMU)-induced rat mammary tumors, the labeled ligand showed a five-fold tumor to muscle (T/M) ratio compared to 99mTc(V)-DMSA (3-fold) and 201TlCl (3-fold). In the case of C(3)H/J virus-induced spontaneous mammary tumors, the differences were not marked. However, in the transplanted rat C(6)-glioma, the T/M ratio of the labeled compound was appreciably higher (four-fold) than that noted with 99mTc(V)-DMSA (two-fold), 201TlCl (three-fold) and 99mTc-citrate (more than three-fold). These findings suggest that the radiolabeled T3,4BCPC may have potential for the detection of cancer. In order to ascertain the efficacy of the compound for photodynamic therapy applications, a preclinical PDT study was carried out in fibrosarcoma-bearing mice after injecting 5.0 mg/kg body weight of the T3,4BCPC. A laser dose of 20 mW for 60 s resulted in 80% destruction of tumors. These data suggest that this molecule could be useful for PDT of cancer. The labeled agent could also be useful in monitoring the progression/regression of tumors before, during, and after chemotherapy, radiation therapy or PDT.     

Evaluation of thallium-201 myocardial emission computed tomography based on a comparison with postmortem findings

The correlative study of myocardial perfusion assessed by 201Tl myocardial ECT with the pathological finding of the heart was performed in 10 autopsied cases with mean age of 77 years old (range: 60-90 y). In 6 cases with myocardial infarction (MI) 7 perfusion defects were observed, that was, 3 in anteroseptal wall, 1 in anterolateral wall and 3 in posterior wall on the images of SPECT. Seven MIs were also found in postmortem examination. Six MIs were observed at autopsy corresponding to perfusion defect on SPECT images. In one myocardial perfusion defect at inferoposterior portion on SPECT, a non-transmural MI was found at anteroseptum. In one case with valvular disease a false positive result was obtained at posterior wall where neither myocardial necrosis nor fibrosis was observed at autopsy. This case had aortic stenosis due to bicuspid aortic valve by autopsy. The ventricle was divided into 16 segments in each of 4 short axial images to evaluate extent of MI. SPECT for extent of MI showed sensitivity of 81.9%, specificity of 96.0% and diagnostic accuracy of 92.5%. False negative segment was apt to be observed at the surrounding of non-transmural MI or basal half of left ventricle (LV) with transmural MI, while false positive segment was at posterior portion of basal half of LV. It was concluded that myocardial ECT was useful for evaluation of the site and extent of MI.     

Evaluation of prognosis in patients with old myocardial infarction--using 201Tl myocardial scintigraphy and 99mTc cardiac scintigraphy

To evaluate the prognosis in 57 patients with old myocardial infarctions, 201Tl myocardial scintigraphy and 99mTc-HSA gated blood pool scan had been done as a 5-year follow up study. We subdivided into two groups; group I (over 60 years) and group II (under 60 years). Cardiac index (CI) and right ventricular ejection fraction (RVEF) did not change significantly, however left ventricular ejection fraction (LVEF) changed significantly (p less than 0.05). Correlationship between CAG score and delta LVEF by handgrip exercise test was y = -1.34 x +3.61 (n = 44, r = -0.400, p less than 0.01). Otherwise, Tl defect ratio between first and final examination did not show the significant change in two groups. In conclusion, nuclear examination (cardiac function and myocardial blood flow) is significant to evaluate the prognosis in patients with myocardial infarction.     

The study of a two-dimensional polar representation of the cardiac SPECT image--a new method of displaying left ventricular wall motion

A new method was developed to display left ventricular wall motion using two dimensional polar representation of cardiac SPECT image. After intravenous administration of 740 MBq (20 mCi) 99mTc (in vivo labeling of red blood cell), ECG-gated SPECT image of cardiac pool was recorded (32 directions, 180 degrees). The short axis images of left ventricle were constructed at end-diastole (ED) and end-systole (ES). Then the functional images of (ED-ES)/ED were calculated at each compatible slices and displayed in color according the degree of wall motion. In 8 cases with cardiac diseases this method was applied and clinically useful functional images could be obtained. The area of akinesia or hypokinesia are successfully demonstrated clearly separated from the area of normokinesia. We conclude that this method is useful to show left ventricular wall motion and to evaluate the segment and grade of abnormal wall motion of left ventricle.     

Sequential changes of the cardiomyopathy in Duchenne muscular dystrophy by 201Tl myocardial SPECT

201Tl myocardial SPECT was performed to evaluate cardiomyopathy in Duchenne type of progressive muscular dystrophy (DMD). Follow up SPECT images of the same patients were also obtained about 1 year after the first scan. Cases subjected to study were 10 DMD. At the first study the hypoperfusion area of the left ventricular muscle was observed in 6 cases (60%) out of 10. At the second study the hypoperfusion areas became wider and lower in 4 out of 6 cases (66.7%). The new hypoperfusion area which was not demonstrated at the first study was observed at the second study in one case of these cases. These results suggested that the positive rate of cardiomyopathy in DMD by 201Tl myocardial SPECT was high, and 201Tl myocardial SPECT is a useful examination to detect the change of myocardial damage in DMD.     

Cerebral blood flow imaging in patients with moyamoya disease

The usefulness of IMP-SPECT and rCBF image by 133Xe inhalation method on rCBF in patients with moyamoya disease was studied. Six patients with moyamoya disease were diagnosed by cerebral angiogram, and STA-MCA anastomosis technique and EMS were done to reconstruct the rCBF. Low perfusion areas were detected around the cerebral infarction and hemorrhage and that of anterior and middle cerebral arteries by IMP-SPECT and 133Xe-rCBF image met by X-ray CT. After surgery, 4 out of 6 cases showed the improvement of rCBF by IMP-SPECT and 133Xe-rCBF image, as for clinical symptoms, there were reduction of TIA in 3 cases, and no rehemorrhage in 3 cases. In summary IMP-SPECT and 133Xe-rCBF image may be useful method to evaluate the rCBF in moyamoya disease and the change of rCBF post STA-MCA anastomosis technique and EMS.     

Clinical evaluation of thyroid imaging with 201T1-chloride.

Clinical value and limitation of thyroid imaging with 201T1Cl were studied. The positive rate of 201T1 was 82% in 22 malignant thyroid lesions and 46% in 37 benign lesions. A 201T1 positive image was obtained when a lesion was parenchymatous and a 201T1 negative one when it was cystic, filled with colloid or hyaline and had massive necrosis or bleeding. Thus 201T1Cl localized in a parenchymatous lesion and did not in a nonparenchymatous one regardless of a malignant or benign disease. An increasing positive lesion in contrast with the surrounding thyroid tissue implies that it may be malignant and a decreasing one benign as a results of review of serial scintiphotos. Scintigraphic methods with 131I and 201T1 are complementary each other and a 201T1 negative image itself has a high diagnostic value but it seems to be better to attach much value to the finding of imaging with 131I when a 201T1 positive image is obtained.     

Spatial and spectral-spatial EPR imaging of free radicals and oxygen in the heart

It has been hypothesized that free radical metabolism and oxygenation in living organs, such as the heart, may vary over particular anatomic locations within these tissues. When there is a lack of tissue perfusion, as occurs during myocardial ischemia or infarction, radical metabolism and oxygenation are greatly changed, however, it was not previously possible to spatially map these alterations within the heart. Therefore, we developed EPR imaging instrumentation to enable three-dimensional spatial as well as spectral-spatial EPR imaging of 2, 3 , or 4 dimensions. Utilizing this instrumentation, at L-band, high quality images of the distribution of nitroxide free radical labels and suspensions of oxygen sensitive chars have been performed on lossy samples of up to 25 mm in size. In the isolated rat heart, imaging experiments were performed to determine the kinetics of radical clearance at different locations within the heart during myocardial ischemia. This kinetic data showed the existence of regional and transmural differences in myocardial radical clearance. In terms of image quality and resolution, we observed with nitroxides that resolutions as high as 1 mm could be obtained, enabling visualization of the of the overall shape of the heart and location of the right and left ventricles. With char suspensions resolutions as high as 0.1 mm were possible, enabling visualization of the ventricles, aortic root, and proximal coronary arteries. Overall our results demonstrate that spatial and spectral-spatial EPR imaging are powerful techniques which enable the visualization of localized differences in free radical metabolism and oxygenation within the heart.     

Myocardial reversibility detection. Rest NTG99mTc-MIBI versus201TI reinjection. Preliminary results

This study test whether sublingual administration of nitroglycerin (NTG) could improve the capability of^99mTc-MIBI to detect reversibility in exercise-induced perfusion defects and to compare it with the²⁰¹TI stress-redistribution-reinjection protocol. Twenty-one patients with previous myocardial infarction were submitted to exercise, rest and NTG rest^99mTc-MIBI imaging (3-day protocol). The patients also underwent exercise, redistribution and reinjection²⁰¹Tl myocardial scintigraphy. A total of 273 myocardial segments were analyzed: 76 (28%) had irreversible defects on stress-rest^99mTc-MIBI, 60 (79%) appeared as fixed defects and 16 (21%) were reversible on NTG rest^99mTc-MIBI. Of the 78 myocardial segments with irreversible defects on standard stress-redistribution thallium cardiac imaging, 63 (81%) did not change and 15 (19%) demonstrated enhanced uptake of thallium after reinjection. Data show that rest NTG^99mTc-MIBI study improves the detection of reversible myocardium versus standard exercise/rest^99mTc-MIBI and achieve similar results than²⁰¹Tl reinjection protocol.     

Usefulness of bone imaging in diagnosis of sternocostoclavicular hyperostosis

Sternocostoclavicular hyperostosis (SCCH) is a rare disease that is characterized by hyperostosis and soft tissue ossification between the clavicles and the anterior part of the upper ribs. There have been few published reports of 99mTc-MDP bone imaging findings in this disease. Thirty-three patients who were suspected to have SCCH were studied with 99mTc-MDP bone imaging. Bone images were abnormal in 31 (94%) of 33 patients. Chest radiographs were available in 30 patients, but negative in 14 (46%) of them. Bone imaging revealed also radionuclide accumulations in other bones such as the vertebrae, femur or sacroiliac joints in ten (14 sites) of 33 cases. Bone scintigraphy was useful in the diagnosis of sternoclavicular hyperostosis.     

Thallium-201 chloride dynamic analysis using thallium-201 chloride and sodium iodide-131 thyroid subtraction scintigraphy

The mechanism of 201Tl chloride accumulation is unclear in thyroid gland and thyroid tumor. This report examines 108 patients that received thyroid scintigraphy examinations with both 201Tl chloride and sodium 131I. The patients were diagnosed clinically and histologically whenever possible. The ROI were obtained by subtraction imaging with both isotopes and by subtraction positive and negative areas of imaging. Dynamic curves were obtained for 201Tl chloride per square unit of each ROI. The dynamic curve in the radioiodide-accumulated area was examined. The data indicate that the clearance rate of 201Tl chloride (T15) was correlated with the sodium 131I uptake rate at 24 h (r = 0.70).     

^9^9^mTcO^3^+和^9^9^mTcN^2^+的二胺基二硫醇配合 物在脑中滞留机制的量子 化学研究

N,N'-二(2-巯乙基)-乙二胺(DTEN)作为二胺基二硫醇类配体的模型化合物,CH~3SH作为还原型谷胱甘肽(GSH)的模拟物,用从头算分子轨道理论研究了这两种配合物与CH~3S^-的反应产物。结果表明,CH~3S^-配位到TcO-DTEN的Tc原子上,而将其转化为不能穿越血脑屏障的[TcO-DTEN-SCH~3]^-离子。与此相反,CH~3S^-不能与TcN-DTEN中的Tc配位,后者仍保持可以穿越血脑屏障的中性分子状态。以此解释了^9^9^mTcO^3^+的二胺基二硫醇配合物比相应的^9^9^mTcN^2^+配合物在脑中有较高的滞留。还用从头算分子轨道理论研究了胺基配体与TcO^3^+及TcN^2^+配位时从胺基N上脱去质子的规律。     

Separation of Tl(I)-Pb(II) by liquid-liquid extraction with diethyldithiocarbamic acid isolation of201Tl

The production of²⁰¹ Tl is described. Natural thallium is irradiated with protons and the induced²⁰¹Pb is separated from the target by liquid-liquid extraction with diethyldithiocarbamic acid in chloroform.²⁰¹Tl is separated from the mother activity (²⁰¹Pb) by liquid-liquid extraction with the same reagent. The decontamination of the final product (carrier free²⁰¹TlCl) is ≥5·10⁶ from the thallium of the target and>5×10⁴ from lead isotopes.     

Scintigraphic imaging of autotransplanted splenic grafts by 99mTc-labeled heat-damaged erythrocytes

Splenectomy is known to increase the risk of bacterial infection. Recently splenic autotransplantation has been suggested as a method of preserving splenic function. In order to demonstrate the viability of transplanted tissue, spleen scintigraphy using 99mTc labeled heat damaged erythrocytes were carried out. So far 21 studies have done in 12 patients. Spleen scans were positive 1 month after surgery, though images showed poor contrast against considerable background of bone marrow and blood pool. The quality of the images much improved five to twelve months after surgery. Functioning splenic autografts could be also shown by scintigraphy using 99mTc sulfur colloid, but the image quality was poorer, particularly within the early stage after operation. Labeling yields were 79.8% on the average, ranging from 45.6-92.3%, that affected little the quality of images. Important techniques in the splenic autotransplantation imaging include a thorough elimination of free 99mTcO4- before injection and to use comparatively small volume of damaged erythrocytes.     

Gamma-ray spectra of 201Tl-radiopharmaceuticals with a scintillation camera--crosstalk of contaminating nuclides of 200Tl and/or 202Tl onto 201Tl-photopeaks

In cardiac imaging with 201Tl, the collimator for low energy high resolution is generally used, and also the energy window, which is set on the spectral display of a pulse height analyzer of a scintillation camera, is chosen 70 +/- 12.5 keV. The purpose of this study is to discuss those conditions in 201Tl imaging with the scintillation camera. Two types of collimators for HR (high resolution) and ME (medium energy) were used in this experiment, and we measured the pulse height spectra of 201TlCl radiopharmaceuticals in air and in a cuboid phantom, connecting a multi-channel pulse height analyzer to the scintillation camera. As a result of measuring of the pulse height spectra, two different energies of gamma rays which are not supposed to emit from 201Tl nuclide were observed, and we also identified the presence of a small amount of 202Tl (with 439 keV) and/or 200Tl (with 368 keV) from their half-life measurements. Thus, the use of the HR-collimator with 201Tl imaging is not suitable, because the shielding effects of its septa is poor to 439 keV gamma-rays, and the scattered radiation produced by the Compton interaction contributes to the principal photopeak on the pulse height spectrum. Here, we recommend the use ME-collimator instead of the HR-one, and of the window width of 76 +/- 25 keV for increasing the count rate.     

Myocardial imaging of patients with myocardial infarction--investigation of diastolic imaging by ECG-gated study

ECG-gated thallium (201T1) myocardial diastolic imaging and non-gated imaging were performed in 22 patients with myocardial infarction. These patients were separated into 2 groups according to echocardiographic findings; Group A: the patients with left ventricular diastolic diameter of 5.5 cm and over and left ventricular ejection fraction of 50% and under; Group B: the others. In the patients of Group A, the low perfusion areas could be demonstrated qualitatively and quantitatively by nongated images as well as gated-diastolic images, while in some patients of Group B, low perfusion areas were shown only by gated-diastolic images, which seemed to be useful. The images gated in 100 ms after the peak of R wave in ECG were conformed as diastolic images by echocardiography, and could be obtained within a half or two thirds of the conventional imaging time.     

Novel oxorhenium and oxotechnetium complexes from an aminothiol[NS]/thiol[S] mixed-ligand system

The simultaneous action of a bidentate aminothiol ligand, LnH, (n = 1: (CH3CH2)2NCH2CH2SH and n = 2: C5H10NCH2CH2SH) and a monodentate thiol ligand, LH (LH: p-methoxythiophenol) on a suitable MO (M = Re, 99gTc) precursor results in the formation of complexes of the general formula [MO(Ln)(L)3] (1, 2 for Re and 5. 6 for 99gTc). In solution these complexes gradually transform to [MO(Ln)(L)2] complexes (3, 4 for Re and 7, 8 for 99gTc). The transformation is much faster for oxotechnetium than for oxorhenium complexes. Complexes 1-4, 7, and 8 have been isolated and fully characterized by elemental analysis and spectroscopic methods. Detailed NMR assignments were made for complexes 3, 4, 7, and 8. X-ray studies have demonstrated that the coordination geometry around rhenium in complex 1 is square pyramidal (tau = 0.06), with four sulfur atoms (one from the L1H ligand and three from three molecules of p-methoxythiophenol) in the basal plane and the oxo group in the apical position. The L1H ligand acts as a monodentate ligand with the nitrogen atom being protonated and hydrogen bonded to the oxo group. The four thiols are deprotonated during complexation resulting in a complex with an overall charge of zero. The coordination geometry around rhenium in complex 4 is trigonally distorted square pyramidal (tau = 0.41), while in the oxotechnetium complex 7 it is square pyramidal (tau = 0.16). In both complexes LnH acts as a bidentate ligand. The NS donor atom set of the bidentate ligand and the two sulfur atoms of the two monodentate thiols define the basal plane, while the oxygen atom occupies the apical position. At the technetium tracer level (99mTc), both types of complexes, [99mTcO(Ln)(L)3] and [99mTcO(Ln)(L)2], are formed as indicated by HPLC. At high ligand concentrations the major complex is [99mTcO(Ln)(L)3], while at low concentrations the predominant complex is [99mTcO(Ln)(L)2]. The complexes [99mTcO(Ln)(L)3] transform to the stable complexes [99mTcO(Ln)(L)2]. This transformation is much faster in the absence of ligands. The complexes [99mTcO(Ln)(L)2] are stable, neutral, and also the predominant product of the reaction when low concentrations of ligands are used, a fact that is very important from the radiopharmaceutical point of view.