Anaphylaxis-like reaction induced by dipyridamole during myocardial scintigraphy.
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Biomedical subjects
Publications and source records attributed to J L Moretti.
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A 59-year-old male underwent a dipyridamole myocardial scintigraphy. During dipyridamole infusion, a marked ST-segment elevation was observed in the inferior leads. After aminophylline injection, a short burst of ventricular tachycardia occurred, then the ST-segment elevation disappeared. The myocardial scintigraphy was consistent with myocardial ischemia of the inferior wall. The coronary angiography revealed no significant coronary lesion. Coronary spasm induced by dipyridamole remained the most probable mechanism for this complication.
3-Bromobenzyloxy phenyloxy hydroxymethyl propanol was labelled with iodine-125. Labeling yield was approximately 92%. Using HPLC and an RP18 column, Iodo*MD (MW = 412) was obtained at no-carrier-added conditions (specific activity 125 Ci/mmole). Biochemical experiments were carried out in vitro and showed a Ki for MAO-B of 5.4 nM and of 5000 for MAO-A (RA/B = 926). Using ex vivo kinetic inhibition in rat (dose: 5 mg/kg p.o.), the results demonstrated a strong similarity of action with BromoMD and IodoMD, with an inhibition percentage that decreased with time (91% at 1 hour, 48% at 8 hours, 2% at 24 hours). The rat brain Iodo*MD concentration was maximal after the first pass and inhibition decreased slowly with time (T1/2 = 1.8 hours). Uptake and wash-out of Iodo*MD was studied on two-day-old rat astrocytes in culture. Half-times of uptake and efflux were respectively 2.5 minutes and 7.5 minutes. The use of metabolic inhibitors (KCN and Digoxin) suggested the absence of any active transport. Binding studies with various concentration of cold MD 360194 showed that at 10(-8) M the uptake decreased significantly. Rats were dissected at different times post i.v. injection (0-2 hours), and the principal organs and brain were obtained (the brain was separated into 7 pieces). Radioactivity was concentrated mainly in the liver (24.6 +/- 4%), fat (12.4 +/- 3.4%) and muscles (18.4 +/- 3%). In the brain the concentration was approximately 1.2 +/- 0.3% within 30 minutes post i.v. injection and 0.84 +/- 0.15% thereafter. The hypothalamus and striatum were two-fold more active than the cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
UNLABELLED: A rapid (25 min) single tracer scintigraphic method to localize parathyroid gland abnormalities was evaluated in 24 patients with hyperparathyroidism. METHODS: Scintigraphy was performed with 99mTc-sestamibi prior to surgery. A 25-min dynamic series centered on the neck was acquired immediately after injection of 99mTc-MIBI. Two planar static views were obtained after 1 and 2 hr. To identify abnormal parathyroid tissue in the thyroid uptake area, a factor analysis of dynamic structure (FADS) was applied to the dynamic acquisition. The results were compared to the analysis of the two planar static views. RESULTS: FADS demonstrated abnormal uptake of the tracer in the thyroid area for 26 of the 31 parathyroid glands found to be abnormal at surgery (5/6 adenomas, 21/25 hyperplastic glands). In three cases, FADS demonstrated parathyroid uptake despite the absence of parathyroid tissue at surgery. FADS revealed as specific and more sensitive than the visual analysis of the two static views, since only 13/30 glands were still visible after 1 hr, and 5/26 after 2 hr. Furthermore, a study with two static views was found to be less sensitive for the detection of hyperplastic glands. CONCLUSION: FADS99mTc-MIBI is performed in less time than existing scintigraphic protocols. It is a promising method to detect abnormal parathyroid glands in the cervical area with a single tracer.
UNLABELLED: The brain distribution of 99mTc-ECD versus 123I-IMP was compared in patients with subacute stroke in order to compare diagnostic accuracy. METHODS: A total of 25 patients with subacute stroke underwent early and delayed SPECT imaging with 99mTc-ECD and 123I-IMP. Washout of 99mTc-ECD was calculated and a differential percentage of activity (DPA) of ischemic versus normal zones was assessed. Images were analyzed twice by five independent observers. RESULTS: Technetium-99m-ECD clearance was 12.5% from the whole brain during early imaging. Ischemic parietal zones had higher clearance than normal parietal zones. Technetium-99m-ECD images showed larger differences between abnormal and normal brain activity than 123I-IMP images. Detection accuracy was slightly, but not significantly, higher for 99mTc-ECD and 123I-IMP (sensitivity: 73.8% as 66.6%; specificity: 81.7% as 81.6%). Reproducibility among observers was similar for 99mTc-ECD and early 123I-IMP. CONCLUSION: Technetium-99m-ECD demonstrates high diagnostic accuracy during subacute stroke, similar to 123I-IMP, but with more intense, better delineation of the perfusion defects.
Single photon emission computed tomography (SPECT) using 99mTc-bicisate and N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP) was compared in 25 patients suffering cerebral ischemia during the subacute phase (7-14 days) of stroke. Patients were classified as cortical strokes (15) and subcortical strokes (10) according to clinical and CT data. Images were analyzed by five independent blinded observers. Then, using a cross-matching method between normal and abnormal brain areas, we evaluated the sensitivity and specificity for 99mTc-bicisate and [123I]IMP and inter- and intraobserver reproducibility. A semiquantitative analysis was performed to compare abnormal hypoactive areas versus the corresponding contralateral areas for 99mTc-bicisate and [123I]IMP in the two patient groups. There was no significant difference for sensitivity and specificity between 99mTc-bicisate and [123I]IMP. Matching was approximately 90% in the two groups. The kappa-concordance index was satisfactory and slightly better for 99mTc-bicisate (0.485) than for [123I]IMP (0.435). Level of hypoactivity in the abnormal areas was significantly higher for 99mTc-bicisate (p < 0.03, n = 25) than for [123I]IMP, especially for cortical strokes. This comparative study demonstrates that 99mTc-bicisate is a very useful tracer for the detection of focal cerebral ischemia by SPECT during the subacute phase of stroke.
UNLABELLED: The radiation dose rate delivered by electron emissions of 99mTc, 123I, 111In, 67Ga and 201Tl was evaluated at the subcellular level. METHODS: Spherical models of sources were used to simulate various cellular localizations of radionuclides. These models were applied to large lymphocytes, assuming uniform distributions of radioactivity throughout the nucleus, the cytoplasm or the cell membrane surface. RESULTS: The graphs of the absorbed dose rate plotted according to the distance from the center of the cell show that the dose rate strongly depends on the subcellular distribution of the radioisotope. The absorbed dose rate D(0) at the center of the cell delivered by a constant cellular radioactivity of 99mTc, 123I, 111In, 67Ga and 201Tl is respectively 94, 21, 18, 74 and 76 times higher if the radioactivity is localized within the cell nucleus than if it is situated only on the cell membrane. D(0) for subcellular localizations was compared to D(0) obtained by assuming uniform distribution of radioactivity throughout the cell. This latter assumption may underestimate the dose rate from 2.8- to 3.2-fold if the tracer is exclusively localized within the nucleus or overestimate from 4.3- to 30-fold if the tracer is localized within the cytoplasm or on the cell membrane, depending on the radionuclide. CONCLUSION: Such findings show that the localization of radiopharmaceuticals at the subcellular level plays a crucial role in determining the actual dose delivered to the cell nucleus in diagnostic nuclear medicine procedures.
Three 125I-iodinated estrogen derivatives; 16 alpha-[125I]iodo-11 beta-methoxy-17 beta-estradiol ([125I]IME2), E-17 alpha-[125I]iodovinylestradiol ([125I]IVE2) and E-17 alpha-[125I]iodovinyl-11 beta-methoxyestradiol ([125I]MIVE2) were synthesized with high specific activities and their binding characteristics and biological effects were analyzed in vitro using the estrogen-receptor-positive human breast cancer cell line MCF-7. Direct and competitive bindings in a whole cell assay indicated that the three derivatives bound to the estrogen receptor (ER) with high affinity. The dissociation constants of the three compounds were higher than the one found for tritiated E2 suggesting that the presence of the methoxy and the vinyl groups decreased the binding affinity. The decreasing affinity order is: [3H]E2 > or = [125I]IME2 > [125I]IVE2 > [125I]MIVE2. The three unlabeled derivatives as well as E2 have been found to activate the vitellogenin promoter fused to the chloramphenicol acetyl transferase reporter gene transfected into MCF-7 cells. This assay showed that the ER is activated in the presence of the three compounds. Unlabeled IME2 produced stimulatory effects similar to those of E2 on MCF-7 growth in vitro. Unlabeled IVE2 and MIVE2 at concentrations lower than 10(-8) M enhanced MCF-7 growth but at a lower level than E2 and IME2 did. Our results clearly indicate that the three derivatives behave like estrogens and that they would be excellent candidates for imaging or monitoring ER-containing breast tumors. Because its affinity for the ER is greatest, IME2 would be the best-suited of the three as a radiotracer.
Heart disease is a rare but important complication of polymyositis. Diagnosis of myocardial disease is usually based on non-specific clinical, electrocardiographic, and echocardiographic data. This paper reports a case of polymyositis with myocardial disease diagnosed by myocardial imaging with radiolabelled antibody to myosin, a specific marker of the necrotic myocardial fibre.
The authors report three cases of acute myocarditis: the first patient was a 23 year old woman treated for tuberculosis who presented with rapidly progressive congestive cardiac failure. The second patient was a 52 year old man with atypical chest pain and the third was a 55 year old woman presenting as an acute myocardial infarction. In all three cases, a positive antimyosin antibody myocardial scintigraphy supported the presumptive diagnosis. The authors review the principles of the method and its potential indications, antimyosin antibody scintigraphy being able to demonstrate recent myocardial necrosis but not to identify the cause. The sensitivity of the technique is high (83 to 100% according to the series) but the specificity is much lower (about 55%) compared with endomyocardial biopsy, an investigation which is specific but not very sensitive. Modifications of the antibody and the radioactive tracer used at present should improve the diagnostic value of the technique in the near future.
In this report, we present the case of a patient suffering from recurrent acute pyelonephritis and who had a hypertrophic right kidney following left nephrectomy. 99mTc-dimercaptosuccinic acid (DMSA) scan is known to be of value in the diagnosis of pyelonephritis, based on the detection of parenchymal abnormalities. The kidney accumulation of 99mTc-mercaptoacetyl-glycylglycylglycine (MAG3) at 2-3 minutes also proves to supply useful information on cortical function. This case illustrates that 99mTc-MAG3 study may be an efficient complementary examination to 99mTc-DMSA scan in the detection and assessment of pyelonephritis.
Myocardial thallium scintigraphy performed after intravenous injection of dipyridamole is a non-invasive method to diagnose and evaluate coronary disease. It can be used as an alternative to postexercise scintigraphy, both methods having similar sensitivity and specificity. The dipyridamole test is contraindicated in patients with a history of bronchospasm and uncontrolled angina pectoris. Close clinical and electrocardiographic monitoring is required. The wide use of tomographic techniques has notably improved this examination.
Para-iodoamphetamines are currently used in nuclear medicine to detect brain perfusion abnormalities with tomoscintigraphy. Little is known about their metabolism pathways in rat and humans. N-isopropyl-125I-iodoamphetamine (IMP) interactions were studied with rat liver microsomes. The first dealkylated metabolite (IAMP) at low concentration gave a type I binding complex then, with a high concentration, a very stable type II complex with oxidized cytochrome P-450 FeIII. In contrast, IMP only gave a type I binding complex in the absence of NADPH. In the presence of NADPH, IAMP and IMP produced 455 nm absorbing complexes, which were enhanced when phenobarbital-treated rat liver microsomes were used. During in vitro metabolic activation, covalent binding of IMP and IAMP on rat liver microsomal proteins was observed. This process was mixed function oxidase (MFO) dependent. The covalent binding level was higher with IAMP and was not affected by flavine oxidase inhibitors. These results confirm the interaction of IMP and IAMP with microsome proteins and cytochrome P-450 and suggest that an N-oxidation of IMP occurs after N-dealkylation. As cytochrome P-450 and dealkylated IMP (IAMP) were found in brain, cerebral metabolism in brain and evolution of activity biodistribution with the course of time can be suggested.
In this article guidelines for single-photon emission computerized tomography (SPECT) of the brain are presented by the Task Group "Neurology" of the European Association of Nuclear Medicine (EANM). Under separate headings are discussed: the pathophysiologic principles of various brain diseases, pharmacokinetics and pharmacodynamics of various radiopharmaceuticals, physical principles of SPECT imaging, computerized data processing, clinical protocols and the evaluation of SPECT results.
To compare the merits of 123I-isopropyl-iodoamphetamine (123I-IMP) and 99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with 123I-IMP and 99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal 99mTc-HMPAO SPECT and abnormal 123I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on 99mTc-HMPAO in areas corresponding to defects on the 123I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination, 99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on 123I-IMP. Crossed cerebellar diaschisis was found in 7 patients with 99mTc-HMPAO and was absent for both 123I-IMP and 99mTc-HMPAO in 3. We suggest that SPECT with 99mTc-HMPAO could show transient hyperemia not demonstrated by 123I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with 99mTc-HMPAO than with 123I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.
p-125I-amphetamine (I-Amp) is retained significantly in liver and lung during brain tomoscintigraphy. To attempt to explain this clinical observation, we have investigated the interaction of I-Amp with rat liver and lung microsomal proteins. Studies using spectral shift technique indicate that low concentration of I-Amp gives a type I complex and high concentration appears very stable type II complex with cytochrome P-450 Fe III. In the presence of NADPH, I-Amp gives rise to a 455 nm absorbing complex with similar properties to the Fe-RNO complexes. This complex formation was greatly enhanced with phenobarbital treated liver microsomes. The in vitro binding study shows that I-Amp and/or its metabolites was covalently bound to macromolecules in the presence of the molecular oxygen and NADPH-generating system. Incubation in the presence of glutathione, cystein and radical scavengers decreases binding. Mixed function oxydase (MFO) inhibitors diminish the amount of covalent binding and alter the extent of metabolite formation. The total covalent binding level increased with liver microsomes from PB pretreated rats as it was observed with the 455nm complex formation. The radioactivity distribution on microsomal proteins was examinated with SDS polyacrylamide gel electrophoresis and autoradiography. This experiment proves that the radiolabelled compounds are bound on the cytochrome P-450. The radioactivity bound increased when the PB induced rat liver microsomes were used. All these results indicate that I-Amp was activated by an oxydative process dependent on the MFO system which suggests a N-oxydation of I-Amp and the formation of reactive entities which covalently bind to proteins.
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Technetium-99m ethyl cysteinate dimer (ECD) has high initial cerebral uptake with slow clearance in nonhuman primates suggesting ideal characteristics for single photon emission computer tomography (SPECT) imaging. We evaluated the biodistribution, dosimetry and scintigraphic pattern of [99mTc]ECD in normal subjects and the accuracy of SPECT imaging in patients with chronic cerebral infarction. Sixteen normal subjects were injected with approximately 10 mCi of [99mTc]ECD. Anterior and posterior single-pass whole-body images were obtained at multiple times after injection. Blood clearance of the radiotracer was rapid, falling to 10.0 +/- 6.6% and 4.9 +/- 1.1% of the injected dose at 2 and 60 min, respectively. Brain uptake was 6.4 +/- 2.1% of the injected dose 5 min after injection. The critical organ was the urinary bladder. Technetium-99m ECD SPECT was performed with a rotating gamma camera in ten of the 16 normal subjects and 34 patients with clinical and CT evidence of chronic stroke. Thirty-three of the thirty-four patients had focal [99mTc]ECD abnormalities on SPECT (97.1%) based on visual inspection of the SPECT images. In summary, we obtained high quality SPECT images as a result of the optimal physical and biologic characteristics of the tracer. Technetium-99m ECD SPECT shows promise for the evaluation of patients with stroke.