The effect of flow on technetium-99m-teboroxime (SQ30217) and thallium-201 extraction and retention in rabbit heart

In order to evaluate the accuracy of blood flow measurement, the single-pass extraction, retention/wash-out and relative net uptake of 99mTc-teboroxime (SQ30217) and 201Tl were evaluated and compared in 20 isolated blood-perfused rabbit hearts at coronary flow rates ranging from 0.49 to 2.85 ml/g wet wt min-1. The average peak extraction of 201Tl (+/- s.d.) (0.67 +/- 0.11) marginally exceeded that of SQ30217 (0.62 +/- 0.12) (p = 0.06). Flow significantly affected the maximum net extraction of 201Tl and the 40-min net extractions of both 201Tl and SQ30217. Unexpectedly, the rate of 201Tl myocardial washout was significantly faster (p less than 0.05) than SQ30217 washout at all flow rates evaluated. Increasing coronary blood flow rate was associated with a more rapid clearance of both tracers from the myocardium (p less than 0.05 for both comparisons). The slope of the linear correlations between relative net SQ30217 uptake versus flow and relative net 201Tl uptake versus flow were found to be similar for up to 10 min after isotope injection. These data were interpreted to indicate that: 1. Thallium-201 might be slightly better extracted than SQ30217. 2. SQ30217 is cleared more slowly from the myocardium. 3. Thallium-201 and SQ30217 appear to be comparable tracers of myocardial perfusion for up to 10 min after injection under the single-pass conditions currently employed. 4. Additional studies are needed to clarify myocardial SQ30217 kinetics.     

Rat model for acute myocardial infarction: application to technetium-labeled glucoheptonate, tetracycline, and polyphosphate.

Cauterization of rat myocardium serves as a quick (2 min) inexpensive technique to create an animal model of acute myocardial infarction useful in evaluating radiopharmaceuticals as potential clinical imaging agents. Preliminary evidence indicates that is correlates well with behavior in man. Application of the model led to the discovery, confirmed by later investigators, that chelating agents such as glucoheptonate and polyphosphate show significant uptake in recent myocardial lesions.     

Comparison of myocardial thallium and beta-methyl iodophenyl pentadecanoic acid (BMIPP) distribution in the cardiomyopathic hamster

The usefulness of fatty acid imaging in the detection of cardiomyopathy was evaluated by comparing thallium and BMIPP myocardial distribution in Bio 14.6 Syrian Hamster (25 week ages). Autoradiography was performed in 3 using 3.7 MBq (100 microCi) of 125I-BMIPP and 37 MBq (1 mCi) of 201TlCl. In vivo pin-hole imaging was performed in 3 using 37 MBq (1 mCi) of 123I-BMIPP and 37 MBq (1 mCi) of 201TlCl. In all cardiomyopathic hamsters decreased uptake of BMIPP compared to that of thallium was demonstrated. These findings suggest dilated cardiomyopathy is associated with severe focal alteration in the substrate used for the performance of myocardial work. In conclusion, myocardial imaging using BMIPP may be useful for early detection of myocardial degeneration compared to thallium in patients with dilated cardiomyopathy.     

Comparative performance of gated perfusion SPECT wall thickening, delayed thallium uptake, and F-18 fluorodeoxyglucose SPECT in detecting myocardial viability

To evaluate the comparative abilities of gated single photon emission computed tomography (SPECT) wall thickening, delayed thallium-201 (Tl-201) SPECT, and F-18 fluorodeoxyglucose (FDG) SPECT in detecting myocardial viability, 23 patients with previous myocardial infarction and clinically suspected viability were studied. Each patient had at least 1 extensive fixed perfusion defect on rest/stress technetium-99m sestamibi SPECT. A total of 41 major vascular territories had fixed defects. The mean (+/- 1 SD) left ventricular ejection fraction determined from gated perfusion SPECT was 26% +/- 11%. Wall thickening was assessed in a semiquantitative fashion by the regional increase in myocardial intensity during systole and was considered normal when a > or = 20% increase was observed. Tl-201 SPECT was acquired 4 hours after resting tracer injection was administered. Viability was considered present when regional defect Tl-201 count density, determined by quantitative analysis, was > 20% greater than that on the resting sestamibi scan. FDG SPECT was performed independently with a 10 mCi F-18 FDG dose after oral glucose loading was performed. A camera equipped with ultrahigh energy collimation was used. Quantitative criteria for viability were the same as for Tl-201. In the 23 patients viability within the fixed sestamibi defects was manifest by preserved wall thickening in 8 patients, delayed Tl-201 uptake in 10 patients, and FDG uptake in 18 patients. Nine major vascular territories with fixed defects were judged viable by wall thickening, 11 by Tl-201 SPECT, and 24 by FDG SPECT (P = .0009). We conclude that FDG SPECT demonstrates more evidence of myocardial viability than either gated sestamibi wall thickening or delayed Tl-201 SPECT.     

Comparison of two three-dimensional gated SPECT methods with thallium in patients with large myocardial infarction

BACKGROUND: Two different commercially available gated single photon emission computed tomography (GSPECT) methods were compared in a population of patients with a major myocardial infarction. METHODS: Rest thallium GSPECT was performed with a 90-degree dual-detector camera, 4 hours after injection of thallium-201 (Tl-201; 185 MBq) in 43 patients (mean age, 62+/-12 years) with a large myocardial infarction (mean defect size, 33%+/-16%). End-diastolic volume (EDV), end-systolic volume (ESV), and left ventricular ejection fraction (LVEF) were calculated by using QGS (Cedars Sinai) and MultiDim (Sopha Medical Vision International, Buc, France). Images were reconstructed by using a 2.5 zoom and a Butterworth filter (order, 5; cut-off frequency, 0.20). LVEF was calculated in all patients by using equilibrium radionuclide angiocardiography (ERNA). EDV, ESV, and LVEF were also measured by using left ventriculography (LVG). RESULTS: Compared with LVG, QGS underestimated LVEF by means of an underestimation of mean EDV. MultiDim overestimated EDV and ESV. GSPECT EDV and ESV overestimation was demonstrated by means of Bland-Altman analysis to increase with left ventricular volume size (P<.05). The difference between LVG and GSPECT volumes was demonstrated by means of regression analysis to be correlated with infarction size. This effect was particularly important with MultiDim (P<.0001). CONCLUSION: In Tl-201 GSPECT, LVEF and volume measurements will vary according to the type of software used.     

A comparison of the technetium-labeled myocardial agents DiArs and DMPE to 201Tl in experimental animals

The biodistribution, kinetics, imaging characteristics and blood flow correlations of ^99mTc labeled DiArs and DMPE were studied. The mice biodistribution were compared to ²⁰¹Tl in mice and dogs, respectively. The myocardial kinetics of these agents were evaluated in normal and ischemic myocardium using miniaturized endocardial detectors. DiArs had a lower myocardial concentration (9.4 ± 0.8% dose/g at 1 min), than DMPE (11.7 ± 1.1% dose/g at 1 min) but both were considerably less than ²⁰¹Tl (23–26% dose/g at 1 min). The kinetic characteristic of both technetium labeled agents suggested that redistribution into ischemic myocardium would not take place, since the clearance rate from normal and ischemic myocardium was similar for both the DiArs and DMPE.The clear visualization of the canine myocardium after i.v. injection demonstrated the superiority of DMPE over DiArs and the potential use of these agents, if proven, to behave the same in human trials.     

Prediction of death, myocardial infarction, and worsening chest pain using thallium scintigraphy and exercise electrocardiography

Although used extensively, there is little published information on the prognostic ability of exercise 201Tl scintigraphy. Accordingly, 1 yr after testing we contacted 819 patients without previous MI or CABG seen in our laboratory during a 2-yr period. Events were defined as death from a cardiovascular cause, nonfatal MI, or worsening clinical state requiring CABG. The event rate was 3.9 events per 100 patients per year. There was univariate prognostic information when comparing the highest and lowest categories as risk ratios for chest pain characteristics (2.7), sex (2.3), exercise duration (3.1), ST slope (2.5), and thallium pattern (11.6), intensity of perfusion defect (17.2), and number of abnormal regions (8.7). However, the strongest predictors were also the least common. Prognostic ability was improved by combining the results categorically, as the number of abnormal tests (13.9). The highest risk ratio, 20.5:1, was obtained by combining results through discriminant function analysis. We conclude that exercise thallium scintigraphy provides prognostic information, although the most predictive patterns are uncommon. Combining the results of multiple test results improves the prognostic ability.     

Experience with 201thallium in detection of myocardial infarction

Our preliminary experimental and clinical results with ²⁰¹Tl myocardial scanning are presented. 48 patients with normal coronary vessels, acute transmural myocardial infarction, localized and diffuse coronary heart diseases and congestive myocardiopathy were investigated. Results of scans and the usual cardiological investigations were in good agreement thus justifying further use of ²⁰¹Tl myocardial scintigraphy as an adjunctive method in cardiology.Presented at the Radionuclide Meeting, Lund/Schweden, June 6./7. 1975.     

Mechanism of thallium extraction in pump perfused canine hearts

Myocardial extraction of Tl has been postulated to depend on the rate of delivery (flow rate) and the metabolic state of tissue (ATPase activity). Experiments were performed to assess the role of these factors. In 22 arrested dog hearts the left anterior descending and circumflex coronary arteries were cannulated and pump perfused with oxygenated blood containing 204Tl. Isotope activity was determined in coronary sinus blood. The myocardial extraction ratio (E) of Tl varied inversely with flow, and the permeability-surface area product (PS) increased with increasing flow rates. These findings indicate that Tl uptake is flow dependent and can be analyzed with Renkin's capillary clearance theory. To assess the role of ATPase in Tl uptake, studies were also performed with blood containing ouabain. After introducing ouabain, coronary sinus blood Tl activity increased, approaching arterial activity, and E fell markedly. It was concluded that myocardial Tl uptake is mediated by ATPase.     

Comparative myocardial uptake characteristics of hexakis (alkylisonitrile) technetium(I) complexes. Effect of lipophilicity

Hexakis (alkylisonitrile) technetium(I) complexes are a new class of cationic, lipophilic myocardial perfusion imaging agents. To further evaluate the effect of lipophilicity on myocardial uptake characteristics, the authors systematically synthesized and tested Tc-isonitrile complexes of varying lipophilicity in both cellular and whole animal systems. In chick heart cells in monolayer culture, cellular plateau level uptake in general correlated with lipophilicity of the complexes (determined by reverse phase high performance liquid chromatography) (r = .71) as well as with scintigraphic intensity of imaged rabbit hearts (r = .91). Exceptions to this trend indicated that additional factors such as size of the complex and form of the terminal alkyl chain branching also may have influenced uptake. The data indicated that neither the lipophilic properties nor the cation charge alone were sufficient to predict myocardial uptake. In addition, intravenous injection of complexes into rabbits showed optimal myocardial images with agents of intermediate lipophilicity. Results indicated that, following intravenous administration, complexes of low lipophilicity yielded suboptimal myocardial images because of low heart cell uptake, whereas complexes of high lipophilicity yielded poor relative myocardial visualization because of excessive binding to additional organs and compartments.     

Quantitative assessment of thallium myocardial washout rate: Importance of peak heart rate and lung thallium uptake in defining normal values

Traditionally, the results of exercise thallium scintigraphy were interpreted by transient defect analysis using initial and delayed images. Recently, washout rate analysis has been used for the relative quantification of exercise thallium scintigraphy. A diffuse slow washout from all myocardial regions has been defined as the indicator of extensive coronary artery disease. However, slow washout has occasionally been observed in normal cases and in healthy myocardial segments which are not supplied by a stenosed artery in patients with single or double vessel disease. We evaluate the factors in fluencing washout rate in 100 normal patients and 63 patients with angina pectoris (33 cases of single vessel disease and 30 cases of double vessel disease). The washout rates were calculated using circumferential profile analysis. In normal patients, washout rate, was closely related to peak heart rate (r=0.72) and inversely related to lung thallium uptake(r=-0.56). A diffuse slow washout was observed in seven (7%) of 100 normal patients, six (18%) of 33 cases of single vessel disease and eight (24%) of 30 cases of double vessel disease. The patients with diffuse slow washout showed significantly higher lung thallium uptake values and lower peak heart rates than those without diffuse slow washout (P<0.01). Thus, this false positive slow washout should be considered in the interpretation of quantitative exercise thallium scintigraphy.     

Quantitative assessment of thallium myocardial washout rate: importance of peak heart rate and lung thallium uptake in defining normal values

Traditionally, the results of exercise thallium scintigraphy were interpreted by transient defect analysis using initial and delayed images. Recently, washout rate analysis has been used for the relative quantification of exercise thallium scintigraphy. A diffuse slow washout from all myocardial regions has been defined as the indicator of extensive coronary artery disease. However, slow washout has occasionally been observed in normal cases and in healthy myocardial segments which are not supplied by a stenosed artery in patients with single or double vessel disease. We evaluate the factors influencing washout rate in 100 normal patients and 63 patients with angina pectoris (33 cases of single vessel disease and 30 cases of double vessel disease). The washout rates were calculated using circumferential profile analysis. In normal patients, washout rate was closely related to peak heart rate (r = 0.72) and inversely related to lung thallium uptake (r = -0.56). A diffuse slow washout was observed in seven (7%) of 100 normal patients, six (18%) of 33 cases of single vessel disease and eight (24%) of 30 cases of double vessel disease. The patients with diffuse slow washout showed significantly higher lung thallium uptake values and lower peak heart rates than those without diffuse slow washout (P less than 0.01). Thus, this false positive slow washout should be considered in the interpretation of quantitative exercise thallium scintigraphy.     

Spatial distribution and temporal changes of pulmonary thallium uptake in myocardial perfusion studies

Spatial distribution and temporal changes in pulmonary thallium uptake were assessed in 24 normal subjects and 35 patients with coronary artery disease (CAD). In studies carried out directly after stress and 3 h later, pulmonary T1 uptake was assessed as body surface area corrected absolute pulmonary uptake in the upper, middle and lower right lung regions, and in the total right lung and upper left lung. Pulmonary/myocardial (PM) uptake ratios for these 5 regions were calculated as mean pulmonary/mean background-corrected myocardial uptake. Additionally, wash-out was assessed for each region and for the myocardium. In normal subjects, the inital pulmonary T1 uptake, the PM ratios and T1 wash-out were greater in the lower lung regions than in the upper. In the late studies, no significant differences in T1 content or PM ratios were found among the regions. In patients with CAD, initial pulmonary T1 uptake and PM ratios were greater in the lower than in the upper regions, and higher than for the normal subjects in all pulmonary regions (P<0.001). T1 wash-out was significantly higher in the low and middle regions versus the upper region (P < 0.001) and higher in all regions than in normal subjects (P<0.001). In the late studies no significant differences in T1 content or PM ratios were found between any pulmonary regions. Pulmonary T1 content was, in all regions, higher in CAD than in normal subjects (P<0.01), as were the PM ratios (P<0.001). In conclusion, in normal subjects as well as in patients with CAD, pulmonary T1 uptake is greatest in the lower lung regions. Absolute pulmonary T1 uptake, PM ratios and pulmonary wash-out are greater in all lung regions in patients with CAD. Lower myocardial uptake may be the more important factor in producing the increased PM ratios in patients with CAD. Pulmonary redistribution is complete after 3–4 h. These characteristics strongly affect pulmonary T1 uptake ratios and wash-out assessments.