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Are right and left ventricular ejection fractions equal? Ejection fractions in normal subjects and in patients with first acute myocardial infarction.

Right and left ventricular ejection fractions (RVEF and LVEF) were determined by radionuclide imaging in 37 normal subjects and 37 patients by means of (1) the traditional way of calculating ejection fraction from first-pass time-activity curves of each ventricle generated from a single fixed ventricular region of interest, (2) dual first-pass time-activity curves generated from the end-diastolic and end-systolic regions, respectively, and (3) the multigated equilibrium method, also applying separate regions in end-diastole and end-systole for each ventricle. Values for RVEF measured by method 2 were significantly higher than values obtained by methods 1 and 3. In normal subjects, the values for RVEF measured by method 2 were equal to the values for LVEF determined by either this method or the equilibrium technique. Methods 1 and 3 had a tendency for underestimation of RVEF, probably because of inclusion of right atrial activity into the right ventricular region of interest. Methods 2 and 3 were applied to measure RVEF and LVEF, respectively, in 153 patients in the second week after first acute myocardial infarction. Among these, 25% had normal ejection fractions, 47% had a decrease in only LVEF, 8% a decrease in only RVEF, and 20% a decrease in both RVEF and LVEF.

Acute Disease↗

Labeling of monoclonal antibodies with radionuclides.

Antibodies, specifically monoclonal antibodies, are potentially very useful and powerful carriers of therapeutic agents to target tissues and diagnostic agents. The loading or charging of antibodies with agents, especially radiotracers, is reviewed here. The choice of radioisotope for immunodetection and/or immunotherapy is based on its availability, half-life, nature of the radiation emitted, and the metabolic pathways of the radionuclide in the body. Most important of all are the derivatization techniques available for labeling the antibody with the given radionuclide. Isotopes of iodine and divalent metal ions are the most commonly used radionuclides. Antibodies labeled with iodine at tyrosine residues are metabolized rapidly in vivo. This leads to the incorporation of metabolized radioactive iodine into various tissues, mainly the thyroid gland and stomach, and to the accumulation of high levels of circulating iodine in the blood, which masks tumor uptake considerably. To overcome these limitations, the use of iodohippurate as an iodine-anchoring molecule to the protein should be considered. When divalent or multivalent metal ions are used as the preferred radionuclide, bifunctional chelating reagents such as ethylenediaminepentaacetic acid (EDTA) or diethylenetriaminepentaacetic acid (DTPA) are first coupled to the protein or antibody. These chelating molecules are attached to the protein by formation of an isopeptide linkage between the carboxylate of the chelating reagent and the amino group of the protein. Several procedures are available to generate the isopeptide linkage. When the anchoring of the chelating agent through isopeptide linkage results in the inactivation of the antibody, periodate oxidation of the carbohydrate moiety of the antibody, followed by reductive coupling of chelator, could be considered as an alternative. There is still a need for better, simpler, and more direct methods for labeling antibodies with radionuclides.

Animals↗

Intravenous digital subtraction angiography in the assessment of patients with left to right shunts before and after surgical correction.

Pre- and postoperative structural changes and pulmonary to systemic flow (QP/QS) ratios were assessed using digital angiography in 34 patients documented to have a left to right shunt at cardiac catheterization. There were 16 men and 18 women whose ages ranged from 4 months to 60 years. The radiographic single mask mode was used for all digital subtraction angiographic studies with a typical radiographic sequence being 80 to 100 kV, 5 to 10 mA/frame at six frames/s for 15 seconds. Renografin-76 was used as a bolus injection at 0.5 to 1.0 ml/kg via an arm vein in most patients. The level of the left to right shunt and any associated anomalies were noted and compared with results from cardiac catheterization. Digital subtraction angiographic flow curves were generated from the pulmonary arteries, and QP/QS ratios were calculated pre- and postoperatively using the gamma variate fit method and compared with the QP/QS ratio from first pass radionuclide studies. A strong correlation between preoperative digital subtraction angiographically derived QP/QS ratio and radionuclide-derived QP/QS ratio was found, with an r value equal to 0.89, p less than 0.0001. Postoperatively, all patients had a QP/QS ratio less than 1.2:1.0 for both digital subtraction angiography and radionuclide studies. The level of left to right shunt was accurately assessed in all patients, and its absence observed postoperatively. Associated anomalies, such as a persistent left superior vena cava, coarctation of the aorta and partial anomalous venous return, were identified in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Clinical applications of 188Re-labelled radiopharmaceuticals for radionuclide therapy.

188Re is a radionuclide in which there is widespread interest for therapeutic purposes because of its favourable physical characteristics. Moreover, it can be eluted from an on-site installable 188W/188Re generator, which has a useful shelf-life of several months. Most of the clinical experiences gained with 188Re concern the use of 188Re-1,1-hydroxyethylidenediphosphonate (188Re-HEDP) for bone pain palliation in patients suffering prostate cancer. The maximum tolerated activity was 3.3 GBq 188Re-HEDP and if the platelet count exceeded 200 x 10(9) l(-1), the administration of 4.4 GBq appeared safe. Evidence for repeated administrations of 188Re-HEDP rather than single injections was established. In general, pain palliation occurs in 60-92% of patients with only moderate transient toxicity, mainly related to changes in blood counts. Also in haematology, radioimmunotherapy by means of 188Re might play a role by selectively targeting the bone marrow in patients undergoing conditioning prior to haematopoetic stem cell transplantation. The feasibility of such an approach was proven using a Re-labelled monoclonal antibody directed toward the CD66-antigen. More recently, encouraging safety data on locoregional treatment of primary liver tumours using 188Re-labelled lipiodol were reported. The normal organs at greatest risk for toxicity are the normal liver and the lungs. About 50% of the patients reported mild and transient side effects, mainly consisting of low grade fever, right hypochondrial discomfort or aggravation of pre-existing liver impairment. Besides the applications in oncology 188Re-based therapies have also been pioneered for benign condition such as prevention of re-stenosis following angioplasty and for radiosynovectomy in cases of refractory arthritis.

Arthritis, Rheumatoid↗

Development of radiocontrast agents for vascular imaging: progress to date.

The revolution in molecular imaging techniques is profoundly changing the understanding of the pathophysiology and treatment of atherosclerosis. With these rapid changes there is an increasing demand for development of sensitive and well tolerated novel imaging agents that can be rapidly translated from small animal models into patients with atherosclerosis. Nuclear medicine and positron emission tomography techniques have the ability to detect and serially monitor a variety of biologic and pathophysiologic processes usually with tracer quantities of radiolabeled peptides, drugs, and other molecules at dosages free of pharmacologic adverse effects unlike the current generation of intravenous agents required for magnetic resonance imaging (MRI) and computed axial tomography (CT) scanning. A representative sampling of the wide array of radiopharmaceuticals developed specifically for radionuclide imaging of atherosclerosis, that have been approved for clinical use and those in pre-clinical trials, have been reviewed in this article. The presence of an inflammatory stimulus increases expression of CC (cysteine-cysteine motif) chemokine receptor (CCR)-2 on monocytes and macrophages, and somatostatin receptors on T lymphocytes. Radiolabeled monocyte chemoattractant protein (MCP)-1 binds with high affinity to CCR-2 and can be used to detect subacute and chronic inflammatory lesions. Similarly, radiolabeled octreotide or depreotide can be used to detect activated T lymphocytes which may identify the vulnerable plaque. Animal models indicate that (99m)Tc-annexin V, (125)I-MCP-1 and [(18)F]-fluoro-2-deoxyglucose are effective in identifying apoptotic cell death, macrophage infiltration and metabolic activity in atheromatous lesions, respectively. Expression of alpha(v)beta(3) integrin is increased in activated endothelial cells and vascular smooth muscle cells after vascular injury, and alpha(v)beta(3) integrin is minimally expressed on smooth muscle cells and is not expressed on quiescent epithelial cells. Radiolabeled high-affinity peptides can be used to target the alpha(v)beta(3) integrin and visualize areas of vascular damage. Advances in technology such as the micro-single photon emission computed tomography (microSPECT) have the potential to overcome the drawbacks of older CT and MRI methodologies, such as lack of biologically relevant ligands and compatible blood pool contrast agents for imaging. Despite these advances in imaging technology, the small size of atheromatous lesions makes it difficult to detect using external imaging techniques. Therefore, recently there has been renewed interest in the use of intravascular catheter-based radiation detectors.

Animals↗

[Non-invasive methods of control of the intestinal motility in surgical practice].

Selective spectral peripheric electrogastroenterography (SSPEGEG), the noninvasive method of the gut functional state estimation, is based on registration of biopotentials from the body surface, generated by stomach and intestine, using apparatus-program unit on the PC IBM base. The possibilities and advantages of this method in comparison with others (roentgenological, radiological, radionuclide, balloonographic and tensiographic) were considered. The principles of the SSPEGEG application for clinical monitoring conduction are adduced.

Digestive System↗

Diagnostic thyroid procedures and corresponding radiation doses in Manitoba: 1981-1985.

Data on nuclear medicine thyroid examinations performed in Manitoba (population 1 million) from 1981-1985 were collected, with more detailed demographic data obtained on 1,100 consecutive patients between June 1987 and January 1988. An average of 2,081 patients were examined per year, 81% female and 19% male, representing 8.4% of all nuclear medicine procedures. Typical administered activity and associated HE per patient were 238.0 MBq and 1.5 mSv for 99mTc, 7.4 MBq and 1.2 mSv for 123I, and 0.33 MBq and 3.9 mSv for 131I. Based on NCRP risk estimates with explicit corrections for age, sex, and radionuclide used, it is estimated that the rate of thyroid cancer induction is unlikely to exceed 0.56 y-1, of which about 10% would be fatal. This estimate is about a factor of 4 less than that generated using more generally applicable radiation protection risk estimates averaged over both sexes and all ages in the general population. The replacement of 131I with the present mix of radiotracers used for thyroid evaluation has resulted in a reduction of the estimated population detriment by a factor of 3.6.

Adolescent↗

Transit time of a radionuclide bolus through inferior vena cava.

The effect of an intrinsic block or extrinsic pressure on blood flow through the inferior vena cava (IVC) was studied after rapid injection of 99mTc-pertechnetate or 99mTc-phytate into the femoral vein. Peak-to-peak transit time (PTT) between the curves generated at IVC origin and over the cardiac blood pool was measured in twelve normal patients (PTT = 2.0 +/- 0.7 s) and six patients clinically suspected of circulatory impediment through the IVC (PTT = 3.0 to 30.0 s). PTT measurements augmented the information obtained from sequential scintiphotos of IVC circulation. It is felt that this may be a more objective parameter for follow-up of patients having a progressive, primary disease of this vessel.

Blood Circulation↗

Estimation of absolute left ventricular volume from gated radionuclide ventriculograms. A method using phase image assisted automated edge detection and two-dimensional echocardiography.

Twenty-four patients underwent gated cardiac blood pool (GBP) imaging, two-dimensional echocardiography (2-D echo), and single-plane contrast ventriculography (within 24 hours). Variable left ventricular (LV) regions of interest on GBP images were identified by an automated threshold radial search. To avoid excluding LV counts we indexed the search threshold to the threshold identified by a phase image generated by Fourier analysis. LV depth calculated by 2-D echo was used for attenuation correction of LV counts. LV end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated by dividing attenuation, background and deadtime corrected LV count rates by the background corrected count rate/ml of venous blood drawn during the study. Correlations between radionuclide and contrast volumes were good (EDV + ESV r = 0.97, EDV r = 0.94, ESV r = 0.95). Regression lines were close to the lines of identity. This method, in which GBP imaging and automated LV edge finding are complemented by 2-D echo for count attenuation correction, demonstrated reliable and reproducible noninvasive estimates of absolute LV volume.

Adult↗

Normal variation in radionuclide esophageal transit studies.

We studied the esophageal transit of aqueous 99mTc-sulfur colloid in 16 normal subjects, 8 of them twice. Condensed dynamic images having a spatial and a temporal dimension fell into four patterns: (1) idealized form, (2) retrograde motion, (3) splitting of the bolus, and (4) generation of a substantial residual component. The retrograde index quantifying retrograde motion in the first swallow (RI), the rapid component mean transit time through the esophagus in the first swallow (MTT), and the residual fractions after the first, second, and fourth swallows [RF(1), RF(2), and RF(4)] were computed. The intrasubject and intersubject variation of the quantitative results suggest that normal subjects have sporadic aberrant swallows with high RI and/or RF(1). RF(2) and RF(4) showed a significant positive correlation with age.

Adult↗

Functional imaging of the brain.

The radionuclide tracer method is unique amongst all other imaging methodologies in its ability to trace organ or tissue function and metabolism. It derives this advantage from the nature of the signal used for image generation, and its single interaction with the organ or system under examination. Physical processes such as electron or proton density assessment or resonance, edge identification, electrical or ultrasonic impedence, do not pertain to the image generation process in nuclear medicine, and if so, only in a rather secondary manner. The nuclear medicine imaging study is primarily a study of the chemical nature, distribution and interaction of the tracer/radiopharmaceutical utilised with the cellular system which requires investigation: the thyroid cells with sodium iodide, the recticular endothelial cells with colloidal particles, the adrenal medulla cells with metaiodobenzylguanidine, and so on. In the two most recent areas of nuclear medicine expansion, oncology (with labelled monoclonal antibodies) and neurology and psychiatry (with a whole new series of lipid soluble radiopharmaceuticals), specific cell systems can also be targeted and hence imaged and investigated. The study of structure as masterly performed by Virchow and all his successors over more than a century, is now definitely the prerogative of such imaging systems which excel with spatial and contrast resolution (x-ray computed transmission tomography, nuclear magnetic resonance imaging, diagnostic ultrasound). However the investigation of function and metabolism (as performed by Claude Bernard, Georg von Hevesy, and so many others), has clearly passed from the laboratory animal protocol and experiment to the direct investigation in man, this being the achievement of the radionuclide tracer methodology. In this article, we review present interest and developments in that part of nuclear medicine activity which is aimed at the study of the neurological or psychiatric patient.

Amines↗

Quantification of infarct size by 201Tl single-photon emission computed tomography during acute myocardial infarction in humans. Comparison with enzymatic estimates.

We prospectively investigated whether 201Tl single-photon emission computed tomography (SPECT) could accurately diagnose the presence and quantify the extent of acute myocardial infarction when compared with infarct size assessed by plasma MB-creatine kinase activity. Thirty patients with enzymatic evidence of infarction were imaged within 12-36 hours of chest pain (mean, 23.4 hours). No patient had a previous infarction, and none underwent intervention seeking to restore coronary patency. Infarct size was quantified with computer-generated polar maps of the myocardial radioactivity and expressed as a percentage of the total left ventricular volume. To assess left and right ventricular performance, blood-pool gated radionuclide angiography was performed immediately after SPECT. All 30 patients had perfusion defects consistent with myocardial infarction. Scintigraphic and enzymatic estimates of infarct size correlated well for the group as a whole (r = 0.78, p less than 0.001, SEE = 9.1) but especially for those patients with anterior infarction (r = 0.91, p less than 0.001, SEE = 7.9). The poor correlation observed in patients with inferior infarction (r = 0.50, p less than 0.05, SEE = 10.0) was believed to be related to the frequent occurrence of right ventricular involvement because SPECT assessed only left ventricular damage, whereas the enzymatic method estimated the myocardial injury in both ventricles. A quantitative index of right ventricular infarct size, derived from the relation between the scintigraphic and enzymatic estimates, had a strong inverse correlation with right ventricular ejection fraction (r = -0.89, p less than 0.001, SEE = 3.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Creatine Kinase↗

A hyperboliod representation of the bone-marrow interface within 3D NMR images of trabecular bone: applications to skeletal dosimetry.

Recent advances in physical models of skeletal dosimetry utilize high-resolution NMR microscopy images of trabecular bone. These images are coupled to radiation transport codes to assess energy deposition within active bone marrow irradiated by bone- or marrow-incorporated radionuclides. Recent studies have demonstrated that the rectangular shape of image voxels is responsible for cross-region (bone-to-marrow) absorbed fraction errors of up to 50% for very low-energy electrons (<50 keV). In this study, a new hyperboloid adaptation of the marching cube (MC) image-visualization algorithm is implemented within 3D digital images of trabecular bone to better define the bone-marrow interface, and thus reduce voxel effects in the assessment of cross-region absorbed fractions. To test the method, a mathematical sample of trabecular bone was constructed, composed of a random distribution of spherical marrow cavities, and subsequently coupled to the EGSnrc radiation code to generate reference values for the energy deposition in marrow or bone. Next, digital images of the bone model were constructed over a range of simulated image resolutions, and coupled to EGSnrc using the hyperboloid MC (HMC) algorithm. For the radionuclides 33P, 117mSn, 131I and 153Sm, values of S(marrow<--bone) estimated using voxel models of trabecular bone were shown to have relative errors of 10%, 9%, <1% and <1% at a voxel size of 150 microm. At a voxel size of 60 microm, these errors were 6%, 5%, <1% and <1%, respectively. When the HMC model was applied during particle transport, the relative errors on S(marrow<--bone) for these same radionuclides were reduced to 7%, 6%, <1% and <1% at a voxel size of 150 microm, and to 2%, 2%, <1% and <1% at a voxel size of 60 microm. The technique was also applied to a real NMR image of human trabecular bone with a similar demonstration of reductions in dosimetry errors.

Algorithms↗

Preparation of cyclotron-produced 186Re and comparison with reactor-produced 186Re and generator-produced 188Re for the labeling of bombesin.

The radioisotopes (186)Re and (188)Re have been extensively investigated for various forms of radiotherapy due to their useful and high-abundance beta particle emissions, low-abundance and imageable gamma-rays, and chemical resemblance to technetium. In addition, (188)Re is available in no-carrier-added (NCA) form from long lived W-188 generators, whereas (186)Re can be produced in large quantities from reactors, although not in NCA form. However, NCA (186)Re can be produced on a cyclotron by a (p,n) reaction on (186)W. The purpose of this study was to compare labeling of the peptide bombesin with these three forms of rhenium radioisotopes. Cyclotron-produced NCA (186)Re was separated radiochemically from enriched (186)W (96.9%) targets using high-purity methyl ethyl ketone (MEK). The resulting (186)Re-MEK was then loaded onto a small alumina column to separate the resulting NCA (186)Re from any remaining (186)W. The experimental levels of impurities associated with (186)Re at the end of the separation process were found to be 5.7 x 10(-6) Ci of (182)Re (0.57%, t(1/2) = 12.7 h) and 1.283 x 10(-5) Ci of (182m)Re (1.28%, t(1/2) = 2.67 days). The radionuclidic purity of the separated (186)Re was found to be 99.6%, whereas the chemical identity was determined by reversed phase high-performance liquid chromatography (RP-HPLC) to be perrhenate ((186)ReO(4)(-)). Generator-produced (188)ReO(4)(-) from a (188)W/(188)Re generator (Oak Ridge National Laboratory) and CA (186)ReO(4)(-) produced from a (185)Re(n,gamma)(186)Re reaction at the University of Missouri Research Reactor (MURR) were used for comparison with the NCA (186)Re in subsequent studies. N(3)S-5-Ava-BBN(7-14)NH(2) conjugates provide flexibility for designing (186,188)Re-labeled conjugates that retain high in vitro and in vivo specificity targeting of GRP receptor-expressing cells. This study showed that the N(3)S-5-Ava-BBN(7-14)NH(2) could be labeled with (186,188)Re following the preconjugation, postmetallation approach. The (186,188)Re(V)O-N(3)S-5-Ava-BBN(7-14)NH(2) complexes were found to form stable complexes following the reduction of perrhenate (Re(VII)O(4)(-)) with stannous chloride at room temperature, as verified by HPLC and stability studies. The radiolabeling yield was found to be >90%. The HPLC chromatograms of (186,188)Re-N(3)S-5-Ava-BBN(7-14)NH(2) complexes revealed two peaks for each conjugate, reflecting the presence of syn- and anti-isomers, which were resolvable by HPLC but re-isomerized on separation. The biodistribution studies showed that the compounds were excreted through the renal and hepatobiliary systems and demonstrated receptor-specific uptake with an average pancreas accumulation of 8.15% ID/g at 1 h postinjection. Administration of cold BBN effectively blocked pancreatic uptake and further reflects the high specificity this conjugate has for the GRP receptors. At low levels of radioactivity, radiolysis effects were not observed. Scale-up may or may not elicit this effect, particularly for the higher energy beta emitter (188)Re. The biodistribution studies demonstrated that the CA and NCA (186,188)Re conjugates behaved similarly, raising the question of whether NCA (186,188)Re is necessary for specific tumor receptor targeting.

Animals↗

A methodology for evaluating the toxicity of radioactive waste and its application to the radioactive waste generated in Pennsylvania.

Communicating with the public on the risks of low-level radioactive waste disposal is difficult due to the lack of comparisons that are understandable to the public. This paper presents a methodology for analyzing the intrinsic toxicity of radionuclides in waste and comparing it to that for soil or other wastes that may contain naturally-occurring radionuclides. The intrinsic toxicity of each radionuclide is normalized by dividing its specific activity in the waste by an appropriate ingestion risk standard, such as the U.S. EPA proposed drinking water limits. To illustrate the usefulness of this method, it was used to analyze Pennsylvania's commercial low-level radioactive waste inventory. The results are presented along with an indication of the usefulness of this method for screening purposes to analyze and identify problematic constituents in various waste streams.

Evaluation Studies as Topic↗

Dynamic, diagnostic, and pharmacological radionuclide studies of the esophagus in achalasia.

The esophagus was evaluated in 15 patients with achalasia by continuous gamma camera imaging following ingestion of a semi-solid meal labeled with 99mTc. The images were displayed and recorded on a simple computerized data processing/display system. Subsequent ciné mode images of esophageal emptying demonstrated abnormalities of the body of the esophagus not reflected by the manometric examination. Computer-generated time-activity curves representing specific regions of interest were better than manometry in evaluating the results of myotomy, dilatation, and drug therapy. Isosorbide dinitrate significantly improved esophageal emptying.

Adolescent↗

High compression of nuclear medicine dynamic studies.

As data compression plays now an important role in the development of medical PACS, a technique has been developed for medical image sequences storage and transmission in order to obtain very high compression ratio: in dynamic nuclear medicine studies it can achieve a compression ratio as high as 100:1 without significant degradation. The implemented technique combines two methods which multiply their effects. In a first step, a principal component analysis (PCA) of the image series is performed. It extracts a limited number of principal components and their associated images. For data compression it is not necessary to perform an oblique factor analysis to estimate the so-called 'physiological functions' and their spatial distributions as in factor analysis of dynamic structures (FADS). In a second step, the principal images are compressed by means of a transform coding procedure: an adaptive block-quantization technique using the 2D discrete cosine transform (DCT) is implemented, followed by a statistical quantization method to encode the DCT coefficients. To reconstruct the principal images, an inverse DCT is applied. Then the original series is computed from the reconstructed images combined with the principal components which have been stored without any modification. The reconstructed series is compared to the original series, as well as the time activity curves generated on different regions of interest (ROI) and the factor estimates obtained using FADS performed on the two series. Method and evaluation are illustrated on an example of first pass radionuclide angiocardiography.

Humans↗

Radiochemical characterization of modified Technegas.

The aim of this study was to characterize modified Technegas, employing radiochemical analyses and qualitative rabbit organ imaging techniques. Electrophoresis, thin layer chromatography and imaging studies, found modified Technegas to behave like sodium [99mTc]pertechnetate (pertechnetate). Our data indicate that modified Technegas is a pertechnetate aerosol, which results from the presence of 3% oxygen in the reaction atmosphere of the Technegas generator.

Animals↗