Viability as seen with radiolabelled fatty acids--a new approach to a challenging problem.
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Animals↗
Biomedical subjects
S N Reske
Publications and source records attributed to S N Reske.
[The noninvasive determination of resting myocardial blood flow in patients using 82 Rb in comparison with the argon method].
Resting myocardial blood flow in absolute units was determined in 11 patients without known heart disease using dynamic PET with 82Rb. Based on a modified Fick's approach to measuring myocardial blood flow, originally developed and validated in canine studies by Herrero and coworkers (Circulation 1990; 82: 1377-86), a global flow value of 0.60 +/- 0.10 ml/min/gr myocardium (MV +/- SD, N = 11) was obtained. With the exception of the apex, segmental blood flow was not significantly different in 12 left ventricular myocardial segments, indicating homogenous myocardial blood flow distribution. In 5 patients global myocardial blood flow was determined simultaneously both by 82Rb PET and argon as inert gas method. 82Rb flow did not differ significantly from argon flow (0.60 +/- 0.05 vs. 0.68 +/- 0.15, MV +/- SD, N.S.). These results show that correct quantitation of resting myocardial blood flow with dynamic 82Rb PET is feasible also in patients.
Adult↗
[Detection of bone involvement in malignant diseases by immunoscintigraphy of the bone marrow].
The results of immunoscintigraphy of haematopoetic bone marrow were compared with those of conventional bone scanning in 141 patients with malignant diseases. Marrow scans showed more metastatic lesions than bone scanning in all patient subgroups, resulting in a significantly more extended skeletal involvement. CT was concordant in 83.3% of 323 skeletal regions with bone marrow scanning. Bone marrow scans of 30 control patients with benign disease were abnormal only in 7 of 2135 skeletal regions in 3 patients. In malignant lymphoma, bone marrow histology or aspiration cytology was concordantly positive in 14 or negative in 17 patients. Immunoscintigraphy of haematopoetic bone marrow provides a reliable, sensitive and safe novel approach towards the non-invasive evaluation of metastatic spread to the skeleton.
Aged↗
Single photon emission tomography imaging of myocardial oxidative metabolism with 15-(p-[123I]iodophenyl) pentadecanoic acid in patients with coronary artery disease and aorto-coronary bypass graft surgery.
A total of 29 patients with coronary artery disease (CAD) were investigated with 15-(p-[123I] iodophenyl)pentadecanoic acid (123I-IPPA) and sequential single photon emission tomography (SPET). Of these, 19 were studied after aorto-coronary bypass graft surgery. Some 13 patients without evidence of CAD served as a control group. Two SPET studies (early and late) were carried out within 45 min after intravenous administration of 200 MBq 123I-IPPA at peak sub-maximal exercise. Semi-quantification of uptake (related to perfusion) and turnover (linked to metabolism) was obtained by segmental comparison of oblique slices. Taking coronary arteriography as the "gold standard", 123I-IPPA scintigraphy had the following figures of merit for sensitivity and specificity in the diagnosis of CAD: for the left anterior descending artery territory 93% and 95%, for the left circumflex artery region 96% and 92%, and for the right coronary artery territory 77% and 92%, respectively. In all, 90% of the reperfused myocardial segments showed an improvement of uptake. Of these, 61% exhibited increased turnover after revascularization and 39% had pathologic turnover and thus a dissociation of improvement of perfusion and oxidative metabolism after surgery.
Adult↗
Recent advances in bone marrow scanning.
Interest in bone marrow scanning has been renewed as the result of the development of radiopharmaceuticals for evaluating specific aspects of bone marrow anatomy, physiology and pathology. This article provides a brief review of bone marrow structure, blood flow and function essential to the understanding of basic principles of bone marrow radionuclide imaging. The prospects and limitations of imaging haematopoietic bone marrow in man using indium 111 chloride, technetium-99m (99mTc)-labelled microcolloid or 99mTc-labelled monoclonal antigranulocytic and antimyelocytic antibodies are discussed in more detail. The technical aspects of bone marrow scintigraphy are presented. Results of more recent studies evaluating bone marrow scanning in circulatory, inflammatory and in systemic haematological disorders are summarized. Special attention is paid to the concept of bone marrow micrometastases and its implications for the follow-up of patients with malignant tumours. Recent results suggest that immunoscintigraphy of bone marrow may provide a novel and sensitive approach for establishing the presence and extent of bone marrow infiltration.
Antibodies, Monoclonal↗
Reduced technetium 99m labelled NCA-95/CEA-antibody uptake in liver due to gentle antibody reconstitution. Technical note.
The influence of reconstituting a murine monoclonal IgG1 antibody kit with pertechnetate technetium 99m on antibody distribution in the liver, spleen and sternal bone marrow of patients was examined. The 99mTc-labelled antibody used is directed against non-specific cross-reacting antigen (NCA-95) and carcinoembryonic antigen (CEA) and has been successfully applied for imaging tissue inflammation and bone marrow scanning. Radioactivity uptake was determined in the liver, spleen, bone marrow and a precordial background region in a consecutive series of 25 patients, examined with an antibody preparation, routinely radiolabelled according to the manufacturer's recommendations and in 14 patients, in whom the antibody was reconstituted with special care, avoiding bubble formation and dropping of buffer into the antibody-containing vial. Gentle compared with routine antibody reconstitution caused a highly significant reduction of the antibody uptake in the liver, as determined by count densities, normalized to injected dose and acquisition time (13.2 +/- 5.5 vs 20.1 +/- 6.0 cpm per pixel, means +/- SD, P = 0.008). The liver to background ratio was reduced from 3.4 +/- 1.4 to 1.9 +/- 0.5 (P less than 0.001). Spleen, sternal bone marrow and precordial background count rates were not significantly affected. These results clearly demonstrate that gentle antibody reconstitution can decrease non-specific antibody uptake in the liver by 34% +/- 6.4% (means +/- SEM). Thus, scan quality is improved, and the potential deleterious camouflage of underlying structures is avoided.
Antibodies, Monoclonal↗
Catabolism of 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) by isolated rat hearts.
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Animals↗
[Detection of bone marrow involvement in breast cancer and malignant lymphoma using immunoscintigraphy of the hematopoietic bone marrow].
Radioimmunoimaging of bone marrow was performed for non-invasive detection of skeletal involvement in 15 patients with carcinoma of the breast and 17 patients with malignant lymphomas. Bone marrow scans were performed by means of a monoclonal 99mTc-labelled antibody, directed against NCA-95 and CEA. The presence and extent of skeletal involvement were controlled by skeletal scintigraphy, plain radiographs and CT; bone marrow biopsies were obtained in 19 patients as well. 20 subjects without suspected malignant disease served as controls. Haematopoietic bone marrow was imaged homogeneously and with high contrast in all controls. 15/15 patients with carcinoma of the breast and 10/17 patients with malignant lymphomas had multifocal bone marrow defects due to skeletal metastases. Bone marrow scans revealed significantly more lesions than skeletal scintigraphy both in carcinoma of the breast (p = 0.027) and malignant lymphomas (p = 0.015). Thus, radioimmunoscintigraphy of bone marrow may provide a new, sensitive approach for non-invasive detection of metastatic spread to the skeletal system.
Adult↗
99Tcm-methoxy-isobutyl-isonitrile SPECT to evaluate a perfusion index from regional myocardial uptake after exercise and at rest. Results of a four hour protocol in patients with coronary heart disease and in controls.
In 70 patients with angiographically confirmed coronary heart disease and in 10 controls, a 4 h exercise (E) (injection of 150 MBq 99Tcm-MIBI) rest (R) (800 MBq) protocol was employed. Of these, 10 patients with 21 myocardial defects after E received a third injection 24 h after. SPECT was used to image myocardial distribution, and visual findings separated three patterns of perfusion defects after E v. R (reversible [REV], partial reversible (PREV), irreversible (IRR)). Relative regional uptake was obtained from a target-like (33 ROIs) evaluation of short-axis cuts, establishing a perfusion index (PI) by relating the defect uptake to individual maximum uptake (100%) after exercise (PIE), at rest (PIR) and the respective differences Delta PI (PIR-PIE, i.e. filling in by the second 99Tcm-MIBI injection). Visually, the sensitivity was 86% in patients or 69% in involved vessels (stenoses of greater than 33%). Vascular supply areas revealed minimal PIE values of 74.7 +/- 10.6% (control), 62.4 +/- 9.2% (REV), 46.1 +/- 7.7% (PREV) and 33.5 +/- 9.9% (IRR) (p less than 0.01). Delta PI was +13.2% or +10.1% in REV or PREV (n.s.) and +2.1% in IRR (p less than 0.01) or -0.2% in controls. PIE values did not correlate to the degree of stenosis. In areas with old myocardial infarction, the same sequence of significant decrease of PIE with reversibility occurred, independent of the patency of the supplying vessel. 33 of 35 IRR defects (94.3%) revealed PIE of less than 45%, thus predicting IRR already after the E examination. PIR values from the 4 h protocol correlated to PIR values 24 h thereafter with r = 0.94 (n = 21). 99Tcm-MIBI may be employed in a short one day E-R protocol in clinical routine. Evaluation of PI seems to be a promising tool to quantify visual defects aimed at describing the perfusional state of the terminal vascular supply area.
Adult↗
Radioimmunoimaging for diagnosis of bone marrow involvement in breast cancer and malignant lymphoma.
Granulopoietic bone-marrow was scintigraphically imaged in 15 patients with carcinoma of the breast and known skeletal metastases, 10 patients with malignant lymphomas, and 15 controls without suspected malignant disease, with a technetium-99m labelled murine monoclonal IgG1 antibody directed against nonspecific cross-reacting antigen (NCA-95) and carcinoembryonic antigen. Immunoscintigraphy revealed more lesions than did bone scanning in both patient groups. This method offers a sensitive, cost-effective, and easy-to-perform whole body technique for evaluating metastatic spread.
Antibodies, Monoclonal↗
Cardiac radionuclide imaging.
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Coronary Disease↗
[Reduced myocardial fatty acid utilization in coronary heart disease following symptom limited ergometric stress. Detection of pathologic metabolic patterns using iodine-123-phenylpentadecanoic acid and sequential SPECT].
Regional cardiac free fatty acid metabolism of 41 patients with coronary artery disease (CAD) and of 10 controls with normal coronary arteries was studied by means of I-123 phenylpentadecanoic acid (IPPA), a radioiodinated palmitic acid analog, and sequential single photon emission tomography (SPECT). All patients and controls underwent symptom--limited bicycle exercise, with the tracer being injected at peak stress. More than 99% of left ventricular segment of controls showed homogeneous tracer uptake and release, indicating homogeneous free fatty acid turnover in normal myocardium. Homogeneous postexercise uptake was followed by decreasing segmental activity in 75.1% of normally perfused segments in patients with CAD. Sixty-five percent and 88.6% of segments, assigned to the perfusion bed of 50%-75% and greater than 75% obstructed vessels had decreased IPPA release and/or reduced IPPA uptake. Patients with exercise induced ischemia had focal metabolic abnormalities in jeopardized myocardium for significantly longer time than clinical or electrocardiographic signs of ischemia (p less than 0.01). All patients with CAD and a negative stress test had metabolic abnormalities, but exhibited, compared to ECG--positive patients, less pronounced segmental metabolic aberrations. These findings indicate reduced cardiac utilization and delayed oxidation of IPPA, associated with exercise-induced ischemia in CAD. The metabolic changes suggest a marked sensitivity to ischemia as well as prolonged postischemic abnormalities of cardiac fatty acid metabolism in jeopardized myocardium.
Angina Pectoris↗
Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) I 123.
The effect of regional myocardial perfusion and flow-independent adrenergic stimulation, as well as lactate-mediated inhibition of cardiac lipolysis, on cardiac IPPA uptake and metabolism was examined in canine hearts (flow studies) and in the isolated perfused Langendorff rat heart (metabolic interventions). In both normal and ischaemic myocardium, local perfusion is a major determinant of cardiac IPPA uptake. In pacing-induced hyperaemia, the strict flow-dependence of cardiac IPPA uptake is not preserved. Adrenergic stimulation raises the rate of oxidation of both palmitic acid 14C and IPPA. This change is reflected by increased metabolite production released into the perfusate and radioactivity clearance recorded externally. Lactate in high concentrations exerts the opposite effect on cardiac free fatty acid oxidation. IPPA is stored in this condition preferentially in tissue phospholipids and triglycerides.
Animals↗
Reticuloendothelial system Fc-receptor function in patients with immune thrombocytopenia after treatment with high dose intravenous immunoglobulin.
Reticuloendothelial system Fc-receptor (FcR) function was measured in 4 healthy controls and 9 patients with immune thrombocytopenia before and after therapy with high dose i.v. gammaglobulin (HDIg). Idiopathic thrombocytopenic purpura (ITP) was diagnosed in 5 patients. 2 patients with hemophilia A, 1 with acute tuberculosis and 1 with psoriasis vulgaris had thrombocytopenia that clinically resembled ITP. 4 out of 9 patients received prednisone prior to or during the study. FcR blockade was observed only in patients with ITP not receiving prednisone. In all other patients, HDIg did not induce a measurable FcR blockade. However, all except 1 patient (with acute tuberculosis) showed a marked rise in platelet counts for 2 to 12 wk. This is consistent with therapeutic efficacy of HDIg in various clinical settings of immune thrombocytopenia. All platelets were fully hemostatic and clinically no difference could be observed. This indicates that the effect of HDIg cannot be due to FcR blockade alone.
Adolescent↗
Experimental basis of metabolic imaging of the myocardium with radioiodinated aromatic free fatty acids.
For the investigation of myocardial perfusion and left ventricular pump function, advanced radioisotopic techniques have been established. New developments in radiopharmacology and single-photon emission computed tomography have recently enabled the investigation of parameters of regional energy metabolism in well defined areas of the heart muscle. For this purpose, various iodine (123I)-labeled free fatty acids (FFA) have been synthesized. The diagnostic application of labeled FFA in heart disease may be important, since FFA are the preferred substrates for cardiac energy production at rest in the fasting state. In addition, regional myocardial FFA uptake and regional myocardial blood flow are tightly coupled in normal myocardium with beta-oxidation which is extremely sensitive to oxygen deprivation. This article outlines the basic physiologic pathways of FFA in normal and ischemic myocardium and reviews the results of animal experiments validating the application of these principles for metabolic imaging of the heart by means of the aromatic radioiodinated FFA, 15-(p-iodophenyl)pentadecanoic acid. In addition, the development, physiologic properties, and potential applications of a new generation of 3-methyl-substituted radioiodinated fatty acids that show high myocardial uptake but prolonged retention are discussed.
Animals↗
[Results of fatty acid SPECT of the myocardium in coronary disease].
New developments in radiopharmacology of 123I-labeled metabolic tracers and single-photon emission computerized tomography (SPECT) allow now-a-days the assessment of parameters of cardiac energy metabolism in well-defined areas of the heart muscle. This article will present a brief outline of the basic pathophysiological principles used in the application of 123I-labeled phenyl fatty acids for the evaluation of CAD. First clinical results suggest an important application of cardiac fatty acid metabolic imaging to the detection, localisation and conceivable quantitation of myocardial ischemia, myocardial infarction and assessment of tissue viability. In addition to the diagnostic applications in CAD, cardiac fatty acid metabolic imaging may provide new perspectives to pathophysiological investigations of the coupling of local flow and substrate utilisation in vivo and the effect of therapeutic interventions.
Coronary Disease↗
Metabolism of 15 (p 123I iodophenyl-)pentadecanoic acid in heart muscle and noncardiac tissues.
The uptake and turnover of omega(p 123I iodophenyl-)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in the heart, lung, liver, kidneys, spleen, and skeletal muscle of rats. At 2 min post injection, a high cardiac uptake of 4.4% dose per gram had already been achieved; this was followed by a rapid, two-component, tracer clearance. The kinetics of tissue concentrations of labeled hydrophilic catabolites indicated a rapid oxidation of I-PPA and the subsequent washout of I-PPA catabolites from heart-muscle tissue. The fractional distribution of the labeled cardiac lipids compared favorably with previously reported values for 3H-oleic- or 14C-palmitic-acid-labeled myocardial lipids. Typical patterns of I-PPA metabolism were observed in tissues depending on primary fatty-acid oxidation, lipid metabolism regulation, or I-PPA-catabolite excretion. The tissue concentrations and kinetics of I-PPA and its metabolites in the heart muscle indicated that general pathways of cardiac-lipid metabolism are traced by this new gamma-emitting isotope-labeled radiopharmaceutical.
Animals↗
123I-phenylpentadecanoic acid as a tracer of cardiac free fatty acid metabolism. Experimental and clinical results.
Metabolism of 15(p-123I-phenyl-) pentadecanoic acid (I-PPA) was investigated in Langendorff perfused rat hearts, fasted Wistar rats, pentobarbital-anaesthetized dogs and, in clinical studies, in patients with coronary artery disease. In murine experiments metabolism of I-PPA was compared quantitatively with 1-14 C-palmitic acid in double tracer studies. In these experiments I-PPA is taken up and metabolized very similarly to palmitic acid. Metabolic intervention studies showed identical directional changes of the rate of cardiac I-PPA and palmitic acid-oxidation during isoproterenol stimulated or lactate-suppressed cardiac lipolysis. Total heart uptake and turnover, as well as kinetics of labelled cardiac lipids, were found to be highly significantly related, when 14C-palmitic acid- and I-PPA-metabolism were analysed in vivo in an identical metabolic environment. In canine experiments initial uptake of I-PPA in the heart muscle is related to regional myocardial blood flow under control conditions and in ischaemia. Pacing induced hyperaemia is associated with an only moderate increase of I-PPA uptake, resulting in a threshold value at flow rates of about 150-200 ml min-1 (100 g-1) In clinical studies, myocardial infarcts can be accurately detected, localized and potentially quantitated. In significant coronary artery disease (greater than 75% diameter reduction), detection rates of 50-75% are found in studies performed at rest. Regional abnormalities of cardiac kinetics of I-PPA were found in about 60% of segments dependent on highly stenosed vessels (greater than 75% diameter reduction).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗