Influence of propranolol on uptake of radioiodinated heptadecanoic acid and thallium-201 in the dog heart

In an experimental study, the influence of propranolol on myocardial uptake of radioiodinated heptadecanoic acid (¹³¹I-HDA) and thallium-201 (²⁰¹Tl) in the dog heart was assessed. Uptake of ¹³¹I-HDA and ²⁰¹Tl was evaluated in ten control dogs and in ten dogs 20 min after IV administration of propranolol (0.15 mg/kg). In both groups, four healthy dogs were studied and six dogs were studied after coronary artery occlusion. It was shown that both total uptake of ¹³¹I-HDA and ²⁰¹Tl did not alter significantly, regardless of significant changes in hemodynamic parameters and total arterial plasma FFA levels. However, distribution of both ¹³¹I-HDA and ²⁰¹Tl was markedly affected by propranolol, since the endocardial to epicardial ratio showed significantly higher values in the ischemic myocardial regions. The results of our study indicate that propranolol (1) preserves myocardial perfusion in the normal and acutely ischemic dog heart, and (2) gives a more favorable distribution in the ischemic myocardial region towards the subendocardial layers.     

External detection of regional myocardial metabolism with radioiodinated hexadecenoic acid in the dog heart

In a previous study we have demonstrated that terminally iodinated hexadecenoic acid (¹³¹I-HA) and Thallium-201 (²⁰¹Tl) are comparable in myocardial uptake and distribution in the ischemic dog heart (Westera et al. 1980). In the present study the potential value of ¹³¹I-HA was proved in determining regional myocardial metabolism in 19 dog experiments.In ten dogs, ¹³¹I-HA was administered 5 min after occlusion of a coronary artery (group II), in six dogs after a 90 min occlusion period (group III). Three dogs served as controls (group I). The turnover rates (t1/2) of ¹³¹I-HA were calculated from mono-exponential time-activity curves, obtained by external detection over ischemic and normally perfused areas during a 30 min period after IV injection of 0.7–1.5 mCi ¹³¹I-HA. The t1/2 values in ischemic regions were found to be significantly longer (group II, 25.1±2.6 min; group III, 22.6±1.8 min) than in nonischemic areas (group II, 12.5±1.8 min; group III, 14.2±1.4 min). The t1/2 values in the control dogs (group I, 13.4±1.4 min) were not significantly different from the turnover rates in the non-ischemic areas of the occluded hearts.We conclude that the study of turnover rates of radioiodinated free fatty acids allows the determination of regional myocardial metabolism and offers a means to distinguish normally perfused from ischemic myocardial tissue.     

Time course of discordant BMIPP and thallium uptake after ischemia and reperfusion in a rat model.

Serial changes in fatty acid metabolism or use associated with acute ischemia and reperfusion were examined in rat hearts. METHODS: Male Wistar rats were subjected to occlusion of the left coronary artery for 20 min followed by reperfusion. After release of the occlusion, groups of animals were allowed to recover for intervals of 20 min (n = 9), 1 d (n = 9), 3 d (n = 6), 7 d (n = 6), or 30 d (n = 6). Hearts were excised 15-20 min after injection of 0.74 MBq of (125)I-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) and 14.8 MBq of (201)Tl. One minute before resection, the left coronary artery was reoccluded and 185 MBq of (99m)Tc-sestamibi were injected to document the area at risk. Triple-tracer autoradiography was performed to assess tracer uptake. Uptake ratios of BMIPP and (201)Tl in the area at risk were calculated on the basis of the count density in the lesion divided by that in the normally perfused area. RESULTS: (201)Tl uptake did not change throughout the observation period (P = 0.25). In contrast, BMIPP uptake increased early in the acute phase (20 min and 1 d), decreased during the subacute phase (7 d), and subsequently recovered in the chronic phase (30 d). CONCLUSION: The present investigation clearly illustrated that BMIPP uptake is higher than (201)Tl uptake in the acute phase, that BMIPP uptake is lower than (201)Tl uptake in the subacute phase, and that BMIPP uptake and (201)Tl uptake are similar in the chronic phase. These results yield data essential to the precise interpretation of BMIPP images.     

Scintigraphy with 201Tl for detection of thyroid cancer metastases

In four patients with disseminated papillary or follicular thyroid carcinoma metastatic sites could be demonstrated by scintigraphy with ²⁰¹Tl. Uptake was present during TSH suppression with thyroid hormone administration. In three of the four cases ²⁰¹Tl scanning revealed metastases while ¹³¹I uptake after triiodothyronine with-drawal was absent. In one patient ²⁰¹Tl demonstrated some metastatic sites while both ¹³¹I uptake and thyroglobulin levels wer negative. Uptake of ²⁰¹Tl in these metastases is at least partially, unrelated to the TSH and thyroglobulin levels or to the ¹³¹I-accumulating capacity. Scintigraphy using ²⁰¹Tl might be helpful for the detection of metastatic thyroid carcinoma in those cases where ¹³¹I uptake is absent.     

Serial changes in 14C-deoxyglucose and 201Tl uptake in autoimmune myocarditis in rats.

This study was designed to examine the relationships between the uptake of 14C-deoxyglucose (DG) and the uptake of 201Tl in a rat model of autoimmune myocarditis. METHODS: Autoimmune myocarditis was induced in normal rats by immunization with pig cardiac myosin. Dual-tracer autoradiography with DG and 201Tl was performed on frozen slices of the animals' hearts 3 wk (acute phase), 8 wk (subacute phase), and 14 wk (chronic phase) (each n = 5) after immunization. The extent of inflammatory damage was classified histologically into three categories on the basis of cell infiltration: mild (Mi), moderate (Mo), and severe (Sv). The regional count in the region of interest set on the autoradiogram was normalized on the basis of that of control rats. The ratio of total cardiac uptake to the injected dose (%ID/g x BW, where ID is injected dose and BW is body weight) was calculated by tissue counting. Expressions of glucose transporters GLUT1 and 4 were evaluated by the enzyme-labeled antibody method. RESULTS: The total cardiac uptake of DG in the acute phase of myocarditis was significantly higher than in normal control rats (3.43% +/- 0.92% vs. 0.97% +/- 0.38%; P < 0.0001); it then decreased in the chronic phase but was still higher than in the controls (1.85% +/- 0.37% vs. 0.97% +/- 0.38%; P < 0.01). The total cardiac uptake of 201Tl in the acute phase of myocarditis was significantly lower than in the controls (7.4% +/- 0.7% vs. 12.0% +/- 3.3%; P < 0.005); it then increased in the chronic phase and reached normal levels (13.0% +/- 3.3% vs. 12.0% +/- 3.3%; not significant [NS]). In the acute phase, the regional uptakes of DG in the Mi, Mo, and Sv regions were 143.1% +/- 107.9%, 169.6% +/- 59.9%, and 317.5% +/- 103.3%, respectively, whereas those of 201Tl were 88.4% +/- 31.9%, 72.1% +/- 34.6%, and 48.4% +/- 21.5%, respectively. GLUT expression was evaluated visually and classified into four grades (0, 1, 2, and 3). In the acute phase, GLUT1 expression was higher in rats in the Sv group than in the controls (2.87 vs. 0.87). GLUT4 was not expressed in the Sv areas but was found in the Mi areas. CONCLUSION: In the acute phase of autoimmune myocarditis in rats, cardiac uptake of DG was accelerated by severe inflammation. Cardiac uptake of 201Tl, on the other hand, was suppressed. Our results suggest that GLUT1 expression accelerates DG uptake by cells in areas of severe inflammation.     

Mechanism of 201Tl uptake in tumours

We have studied the mechanism of tumour uptake of 201Tl by in vivo and in vitro studies. In a series of patients with breast cancer (n = 26), lung cancer (n = 56) and lymphoma (n = 15), the time course of tumour uptake of 201Tl paralleled that in the myocardium with almost identical times of peak uptake being obtained in tumours and myocardium. In a patient with hepatic metastases from colonic cancer undergoing laparotomy, 99mTc labelled microspheres and 201Tl were injected into the hepatic artery and biopsies of metastatic and normal liver tissue obtained. The tumour to normal liver activity ratios for 201Tl were one tenth of those for 99mTc microspheres. In the final part of the study, cells from a lung cancer tissue culture line were incubated for 30 min with 201Tl with and without the addition of cardiac glycoside, which acts a sodium potassium pump blocker. The cells exposed to the cardiac glycoside showed markedly decreased uptake of 201Tl compared to the cells not so exposed (0.6% +/- 0.1% vs 11.8 +/- 0.7.2% of the administered dose). The mechanism of 201Tl uptake of tumours is similar to that in the myocardium. Sodium potassium pump activity appears to be more important than tumour blood flow. 201Tl uptake may provide a useful means of studying tumour viability.     

Serial changes in BMIPP uptake in relation to thallium uptake in the rat myocardium after ischaemia

Several clinical studies have shown that iodine-123 labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) uptake is often lower than the uptake of perfusion tracers in patients with ischaemic heart disease. However, BMIPP accumulation may not decrease during the acute phase of a stunned myocardium in patients with acute coronary syndrome. We evaluated serial changes in BMIPP and perfusion tracer uptake in the myocardium after ischaemia. We performed a 20-min left coronary artery occlusion followed by reperfusion in male Wister rats. One hour after the reperfusion, echocardiography was performed. Intravenous injection of iodine-125 labelled BMIPP and thallium-201 was performed 1 day (acute group) and 5 days (subacute group) after the operation. To determine the myocardial distribution of ¹²⁵I-BMIPP and ²⁰¹Tl, dual-tracer autoradiography was conducted. We identified regions of interest in the anterolateral wall as an area at risk and in the inferoseptum as a remote control area. The anterolateral wall/inferoseptum ratio (A/I ratio) was calculated to compare the distributions of ¹²⁵I-BMIPP and ²⁰¹Tl. Coronary occlusion induced hypokinesia in the anterolateral region 1 h after the reperfusion. The A/I ratio of ¹²⁵I-BMIPP was significantly higher than that of ²⁰¹Tl in the acute group (1.01±0.15 vs 0.80±0.23, P<0.001). On the other hand, there was no significant difference between the A/I ratios of ¹²⁵I-BMIPP and ²⁰¹Tl in the subacute group (0.88±0.18 vs 0.85±0.18). Two rats showed a significantly lower A/I ratio of ¹²⁵I-BMIPP than ²⁰¹Tl in the subacute phase. These data suggest that BMIPP uptake is preserved despite a decrease in perfusion in the acute phase after ischaemia. In the subacute phase, on the other hand, BMIPP uptake is similar to or even lower than thallium uptake. Since BMIPP uptake may change with time after ischaemia, careful interpretation of BMIPP uptake after ischaemia is required in a clinical setting.     

Kinetic analysis of 18F-fluorodihydrorotenone as a deposited myocardial flow tracer: comparison to 201Tl.

The goals of this investigation were to assess the accuracy of (18)F-fluorodihydrorotenone ((18)F-FDHR) as a new deposited myocardial flow tracer and to compare the results to those for (201)Tl. METHODS: The kinetics of these flow tracers in 22 isolated, erythrocyte- and albumin-perfused rabbit hearts were evaluated over a flow range encountered in patients. The 2 flow tracers plus a vascular reference tracer ((131)I-albumin) were introduced as a bolus through a port just above the aortic cannula. Myocardial extraction, retention, washout, and uptake parameters were computed from the venous outflow curves with the multiple-indicator dilution technique and spectral analysis. RESULTS: The mean +/- SD initial extraction fractions for (18)F-FDHR (0.85 +/- 0.07) and (201)Tl (0.87 +/- 0.05) were not significantly different, although the initial extraction fraction for (18)F-FDHR declined with flow (P < 0.0001), whereas the initial extraction fraction for (201)Tl did not. The washout of (201)Tl was faster (P < 0.001) and more affected by flow (P < 0.05) than was the washout of (18)F-FDHR. Except for the initial extraction fraction, (18)F-FDHR retention was higher (P < 0.001) and less affected by flow (P < 0.05) than was (201)Tl retention. Reflecting its superior retention, the net uptake of (18)F-FDHR was better correlated with flow than was that of (201)Tl at both 1 and 15 min after tracer introduction (P < 0.0001 for both comparisons). CONCLUSION: The superior correlation of (18)F-FDHR uptake with flow indicates that it is a better flow tracer than (201)Tl in the isolated rabbit heart. Compared with the other currently available positron-emitting flow tracers ((82)Rb, (13)N-ammonia, and (15)O-water), (18)F-FDHR has the potential of providing excellent image resolution without the need for an on-site cyclotron.     

Myocardial uptake of thallium and rubidium during alterations in perfusion and oxygenation in isolated rabbit hearts

The comparative effects of altered cellular function and coronary perfusion on myocardial 201Tl and 83Rb uptake were evaluated in three groups of isolated rabbit hearts having isovolumic contractions. Paired-indication dilution experiments were performed with 201Tl, 83Rb, and 111In-labeled albumin as an intravascular reference marker. In Group A hearts (n = 12), isotope transport was determined during control, hypoxia, and ischemia. In Group B hearts (n = 8), isotope transport was measured at control flow and again at a 50% and 80% reduction. In Group C hearts (n = 8) only 201Tl uptake was determined at control and following coronary reperfusion. Myocardial 201Tl and 83Rb transport were not significantly different and were proportional to flow. Although all interventions caused significant hemodynamic alterations, neither tracer was affected by hypoxia at constant flow. Thallium-201 permeation, however, was transiently decreased immediately after coronary reperfusion. We conclude that myocardial uptake of 201Tl and 83Rb are similar and directly related to flow, but do not reflect hypoxia induced cellular dysfunction.     

Repeated 131I treatment of a residual ovarian teratoma containing malignant thyroid tissue

A 49-year-old woman with ovarian teratoma received 131I treatment three times for an unresectable mass containing malignant thyroid tissue after surgery. Repeated 131I treatment effectively reduced serum thyroglobulin (Tg) level and tumour uptake of 131I, despite absence of any change in size of the treated tumour. Treatment did not inhibit the increase of serum CA-125 and tumour 201Tl uptake, associated with progression of a radioresistant intratumoral hyper-perfused tissue component, detected by colour Doppler ultrasound. Serum CA-125 level and tumour 201Tl uptake were not significantly changed despite temporary increases in serum Tg level after each 131I treatment. These observations indicate the importance of diagnostic measures using combined functional imaging and tumour markers in managing this rare tumour.     

Prediction of improvement in global left ventricular function in patients with chronic coronary artery disease and impaired left ventricular function: rest thallium-201 SPET versus low-dose dobutamine echocardiography

Accurate assessment of myocardial viability permits selection of patients who would benefit from myocardial revascularization. Currently, rest-redistribution thallium-201 scintigraphy and low-dose dobutamine echocardiography are among the most used techniques for the identification of viable myocardium. Thirty-one consecutive patients (all men, mean age 60 +/- 8 years) with chronic coronary artery disease and reduced left ventricular ejection fraction (31% +/- 7%) were studied. Rest 201Tl single-photon emission tomography (SPET), low-dose dobutamine echocardiography and radionuclide angiography were performed before revascularization. Radionuclide angiography and echocardiography were repeated after revascularization. An a/dyskinetic segment was considered viable on 201Tl SPET when tracer uptake was >65%, while improvement on low-dose dobutamine echocardiography was considered a marker of viability. Increase in global ejection fraction was considered significant at > or = 5%. In identifying viable segments, rest 201Tl SPET showed higher sensitivity than low-dose dobutamine echocardiography (72% vs 53%, P<0.05), while specificity was not significantly different (86% vs 88%). In 17 patients, global ejection fraction increased > or = 5% (group 1) while in 14 it did not (group 2). A higher number of a/dyskinetic segments were viable on 201Tl SPET in group 1 than in group 2 (2.6 +/- 1.9 vs 0.6 +/- 1.2, P < 0.005), while no significant differences were observed on low-dose dobutamine echocardiography (1.7 +/- 1.6 vs 1.1 +/- 1.6). A significant correlation was found between the number of a/dyskinetic segments viable on 201Tl SPET and post-revascularization changes in ejection fraction (r = 0.52, P < 0.05), but such a correlation was not observed for low-dose dobutamine echocardiography. Using as the cut-off the presence of at least one viable a/dyskinetic segment, rest 201Tl SPET had a higher sensitivity (82% vs 53%, P = 0.07) and showed a trend towards higher accuracy and specificity (77% vs 58%, and 71% vs 64%, respectively) as compared with low-dose dobutamine echocardiography. In conclusion, these findings suggest that when severely reduced global function is present, rest 201Tl SPET evaluation of viability is more accurate than low-dose dobutamine echocardiography for the identification of patients who will benefit most from revascularization.     

Correlation of thallium-201 uptake with proliferating cell nuclear antigen in brain tumours

The aim of this study was to assess the correlation between thallium-201 (201Tl) uptake and proliferative activity measured using the proliferating cell nuclear antigen labelling index (PCNA-LI) in brain tumours. Twenty-nine patients with brain tumours were included in this study. Of these, seven were diagnosed with meningioma, 13 had high grade glioma (HGG) and nine had low grade glioma (LGG). A 210Tl single photon emission computed tomography study was performed on all patients before operation, and 201Tl uptake index (UI) and retention index (RI) values were calculated. Cell proliferation was determined by PCNA. While all of the HGGs and meningiomas showed intense 201Tl accumulation on visual interpretation, eight of the nine LGGs did not show accumulation of 210Tl at the tumour site. 201Tl UI values were 3.23+/-0.89 and 2.67+/-0.66 in HGG, 1.27+/-0.18 and 1.23+/-0.09 in LGG, and 4.35+/-1.60 and 2.52+/-0.78 in meningioma on early and delay images, respectively. There was a statistical difference between the 201Tl UI in HGG and LGG. PCNA-LI values were 16.72+/-6.15%, 1.63+/-0.81% and 2.00+/-1.88% in HGG, LGG and meningioma, respectively. The PCNA-LI in HGG was significantly higher than in LGG and meningioma. While the correlation coefficient between the 201Tl UI and the PCNA-LI was 0.94 in gliomas (n=22), there was no correlation in meningiomas. No statistically significant correlation was found between the RI and the PCNA-LI in gliomas. The presence of a strong positive correlation between 201Tl uptake and PCNA-LI indicates that 201Tl uptake can predict the proliferative activity of the glioma.     

Comparison of (18)F-FDG, (131)I-Na, and (201)Tl in diagnosis of recurrent or metastatic thyroid carcinoma.

There are several reports about the usefulness of (18)F-FDG PET in thyroid cancer. However, few studies have compared FDG PET with (131)I and (201)Tl scintigraphy. The aim of this study was to evaluate the clinical significance of whole-body FDG PET in differentiated thyroid cancer and to compare the results with those obtained from (131)I and (201)Tl scintigraphy. METHODS: Whole-body FDG PET was performed on 32 patients (10 men, 22 women; age range, 30-77 y; mean age, 54 y) with differentiated thyroid cancer (5 cases of follicular cancer and 27 of papillary cancer) after total thyroidectomy. An overall clinical evaluation was performed, including cytology, thyroglobulin level, sonography, MRI, and CT, to allow a comparison with functional imaging results for each patient. Metastatic regions were divided into five areas: neck, lung, mediastinum, bone, and other. Multiple lesions in one area were defined as one lesion. The tumor-to-background ratio (TBR) was measured for the lesions that were positive for both (201)Tl uptake and FDG PET uptake. RESULTS: The number of lesions totaled 47. Forty-one (87%) were detected by all scintigraphic methods. FDG uptake was concordant with (131)I uptake in only 18 lesions (38%). FDG uptake was concordant with (201)Tl uptake in 44 lesions (94%). Only one lesion was negative for FDG uptake and positive for (201)Tl uptake, and two lesions were positive for FDG uptake and negative for (201)Tl uptake. A significant correlation was seen between the TBR of (201)Tl and that of FDG (r = 0.69; P<0.05). CONCLUSION: These data indicate that for detecting metastatic lesions, FDG PET and (131)I scintigraphy may provide complementary information, whereas FDG PET may provide results similar to those of (201)Tl scintigraphy. Thus, the combination of (131)I scintigraphy and FDG PET (or (201)Tl scintigraphy) is the method of choice for detecting metastatic thyroid cancer after total thyroidectomy.     

Effects of ouabain on 201Tl and 99mTc MIBI kinetics in rat myocardium--in vivo study using miniature CsI detector]

The aim of this study is to investigate the effect of ouabain (inhibitor of Na-K ATPase) in the myocardial uptake and clearance of 201Tl and 99mTc MIBI using rats. Time activity curves of three groups were measured by CsI miniature detector for 15 min after the administration of each radiopharmaceutical. Groups were divided as follows; 1) control group (CON group), 2) early phase as 15 min after the administration of ouabain (OU15 group), and 3) late phase as 120 min after the administration of ouabain (OU120 group). Main organs of rats including myocardium were resected at 1 min and 15 min after the administration of 201Tl or 99mTc MIBI under the anesthesia of pento-barbital sodium. The uptake (%ID/g) of 201Tl or 99mTc MIBI was measured by well type scintillation counter. The uptake of 201Tl of OU15 group was significantly higher than CON group (OU15: 10.81 +/- 1.90, CON: 1.86 +/- 0.42) and cleared more rapidly. On the contrary, OU120 group showed lower uptake (1.70 +/- 0.21) and slower clearance than OU15 group. Time activity curve of OU15 group indicated the accelerated washout compared with CON group. However, OU120 group showed significantly the reduced washout (CON group: 19%, OU15 group: 22%, OU120 group: 9%). On the other hand, the uptake and time activity curves of 99mTc MIBI were not influenced by ouabain administration. In conclusion, myocardial uptake and clearance of 99mTc MIBI were not related to Na-K ATPase activity, while those of 201Tl were markedly influenced by Na-K ATPase.     

Thallium-201 scintigraphic quantitation of regional flow disparity and subsequent redistribution in dogs

Although quantitative analysis of postexercise thallium-201 (201Tl) scintigrams has been employed clinically for the diagnosis of coronary disease, the precise relationship of the quantitated defects to microsphere determined blood flow has not been determined. Accordingly, 201Tl was injected during exercise in 12 control dogs and seven with left circumflex (LCf) artery stenosis. Gamma camera scanning was started 10 min after 201Tl injection and continued for 3 hr. In the control animals, scintigraphic 201Tl activities in left anterior descending (LAD) and LCf perfusion territories were equal 10 min after 201Tl injection and the loss of 201Tl activity over 3 hr was 54.3 +/- 3.4% and 57.0 +/- 3.6% (mean +/- s.e.e.) of initial LAD and LCf activity, respectively (p = N.S.). In the experimental group, LCf activity 10-14 min after 201Tl injection averaged 67.4 +/- 5.9% of LAD activity in the same heart (p less than 0.001). Furthermore, LCf activity in the experimental animals was significantly lower than LCf activity in the control dogs (p less than 0.005), while LAD activities were not different in the two groups. The ratio of LCf/LAD scintigraphic 201Tl activity immediately after exercise was linearly related to, but higher than, the ratio of regional blood flows at peak exercise (r = 0.88, p less than 0.001) as determined by microsphere injection. Scintigraphic redistribution was also correlated with directly measured redistribution determined by well counter analysis (r = 0.83, p less than 0.025). Thus, in this exercise model, quantitative 201Tl scintigraphy accurately assessed the initial postexercise flow disparity and subsequent redistribution.     

Effects of grisorixin on the distribution of thallium-201 and on the oxidative metabolism in cultured myocardial cells

Previous experiments in the dog and guinea-pig have shown that grisorixin, a monocarboxylic ionophore, can significantly increase the coronary blood flow and the myocardial uptake of 201Tl, as well as have a stimulant effect on the heart. In this study, cultures of myocardial cells were used in order to isolate the cells from the vascular and extracardiac influences so that any ionophorous effect on 201Tl could be evidenced. The effects of grisorixin on the oxidative metabolism were simultaneously studied. The technique described by Harary was used to prepare the cultures. The activity of the 14CCO2 produced by oxidation of [14C]glucose and [14C]octanoate added to the medium of culture and the intra/extracellular ratio of 201Tl concentrations (Tl i/e) were measured. In the controls (n = 8), the Tl i/e was 40 +/- 10 while it was 17 +/- 6 (p less than 0.05) in the cells that received 201Tl and grisorixin at the same time (n = 4), and 19 +/- 5 (p less than 0.05) in the flasks where 201Tl was injected after grisorixin (n = 7). A significant decrease of the [14C]octanoate oxidation was found in the flasks treated with grisorixin (n = 4, -50 +/- 16%, p less than 0.01) while the [14C]glucose oxidation was not significantly lowered (n = 3; -11 +/- 12%). The conclusion is that grisorixin decreases both the intracellular concentration of 201Tl and the fatty-acids oxidation in cultured myocardial cells. The beneficial effects previously observed in vivo were probably the consequence of the strong coronary dilatation and of an indirect stimulation.     

Compartmental modeling of technetium-99m-labeled teboroxime with dynamic single-photon emission computed tomography: comparison with static thallium-201 in a canine model

Di Bella EVR, Ross SG, Kadrmas DJ, et al. Compartmental modeling of technetium-99m-labeled teboroxime with dynamic single-photon emission computed tomography: Comparison with static thallium-201 in a canine model. Invest Radiol 2001;36:178-185.RATIONALE AND OBJECTIVES: A compartmental modeling approach to deriving kinetic parameters from a time series of single-photon emission computed tomography (SPECT) images of technetium-99m-labeled (99mTc-) teboroxime may have value for semiquantitative assessment of myocardial perfusion. This study investigated the value of the kinetic parameters derived from a two-compartment model of 99mTc-teboroxime for measuring myocardial perfusion and compared it with static thallium-201 (201Tl) uptake and microsphere-measured blood flow in dogs. METHODS: Experiments were successfully conducted in 9 of 11 open-chest dogs. During adenosine stress, a single complete set of projections of 201Tl uptake was acquired. 99mTc-teboroxime was then injected during adenosine stress, and a complete set of projections was acquired every 5.7 seconds for 17 minutes. Resting studies were performed on 4 of the animals. All of the projection sets were reconstructed with an iterative algorithm and incorporated corrections for attenuation and the geometric response of the collimators. Regional kinetic parameters (washin and washout) were determined semiautomatically from the time series of reconstructed 99mTc-teboroxime images and registered with microsphere data. Regional washin estimates were compared with 201Tl intensities and myocardial blood flows determined from microspheres. RESULTS: Optimally scaled 99mTc-teboroxime washin parameters and 201Tl uptakes were correlated with microsphere-determined blood flows (r = 0.91, y = 0. 99x + 0.01, and r = 0.92, y = 0.88x + 0.28, respectively). In six of the studies, the left anterior descending coronary artery was occluded, and stress occluded-to-normal (O/N) ratios were calculated. The O/N ratios were 0.32 +/- 0.17 as determined from microspheres injected with 201Tl and 0.38 +/- 0.29 from microspheres injected with 99mTc-teboroxime (P = NS). The O/N ratios were 0.48 +/- 0.16 for static 201Tl uptake and 0.27 +/- 0.21 for 99mTc-teboroxime washin (P < 0.05). CONCLUSIONS: Both 201Tl uptake and 99mTc-teboroxime kinetic parameters were well correlated with flow. The 99mTc-teboroxime washin parameters offer semiquantitative flow values and provide greater defect contrast than can be obtained with 201Tl uptake values.     

Estimation of left ventricular mass in normal and infarcted canine hearts using thallium-201 SPECT

A new automated edge detection program has been developed to estimate left ventricular mass from single photon emission computed tomographic (SPECT) 201Tl images and 14 dogs were studied. Six of the 14 dogs underwent imaging before and 5 hr after coronary artery occlusion with a closed-chest technique. True left ventricular mass was determined at time of killing within 1 hr of the last 201Tl study. Left ventricular mass determined by tomography correlated well with autopsy left ventricular mass (r = 0.94; p less than 0.001, s.e.e. = 5.9 g) over a range of 62-156 g. The intraobserver variation between repeated measurements of the same SPECT study yielded an r = 0.99; p less than 0.0001; s.e.e. = 2.3 g. The reproducibility of the mass determination was assessed in four animals with two studies performed 10-14 days apart. The estimate of left ventricular mass from the two studies were highly correlated (r = 0.98; p less than 0.001) with a mean absolute difference of 4 g (3.3%). In the six dogs with a control and postinfarct study the mean total left ventricular mass by 201Tl tomography varied by less than 3.8% (r = 0.89; p less than 0.001). In conclusion, tomographic imaging with 201Tl can define left ventricular mass accurately and reproducibly in the dog model. The ability of this 201Tl tomographic left ventricular mass program to measure both normal and infarcted tissue accurately suggests the possibility of documenting interventions designed to alter left ventricular mass and of sizing acute infarcts and assessing interventions that may alter acute infarct size.     

A comparison between terminally radioiodinated hexadecenoic acid (*I-HA) and 201Tl-thallium chloride in the dog heart

The regional myocardial distribution of ¹³¹I-16-iodo-9-hexadecenoic acid (¹³¹I-HA) and ²⁰¹Tl-thallium chloride (²⁰¹TlCl) was determined in normal dogs and after occlusion of a coronary artery. The uptake of ¹³¹I-HA was about 20% lower than that of ²⁰¹TlCl but the ratio ²⁰¹Tl/¹³¹I was the same for the whole myocardium within narrow limits for normal as well as infarcted tissue. The potential of ¹²³I-HA as a radiopharmaceutical for diagnosis of myocardial defects is discussed.Dept. Internal Medicine, Head Prof. Dr. C. van der MeerDept. Cardiology, Head Prof. Dr. J.P. RoosDept. Physiology, Head Prof. Dr. A.A. Knoop     

Evaluation of histopathological differentiation in lung adenocarcinoma patients using 201Tl-chloride and 99Tcm-MIBI SPET

The purpose of this prospective study was to evaluate the relationship between thallium-201 chloride (201Tl) and technetium-99m hexakis 2-methoxyisobutylisonitrile (99Tcm-MIBI) accumulation and histopathological differentiation in primary lung adenocarcinoma. A total of 43 patients with primary lung adenocarcinoma were investigated. The patients were divided into well differentiated (n = 17), moderately differentiated (n = 14) and poorly differentiated (n = 12) carcinoma groups. Simultaneous dual single photon emission tomography (SPET) images with 201Tl and 99Tcm-MIBI were acquired 15 min (early) and 2 h (delayed) after injection. Using a region of interest technique, the tumour-to-normal lung ratio was calculated for both early (early ratio) and delayed (delayed ratio) images. The retention index was calculated using the formula delayed ratio/early ratio. Uptake of the radionuclides was compared with the classification of tumour differentiation grading. The mean (+/- SD) values of the early ratio, delayed ratio and retention index using 201Tl were 2.19+/-0.72, 2.28+/-0.71 and 1.06+/-0.16, respectively, in the well differentiated group, 2.38+/-0.83, 2.48+/-0.84 and 1.08+/-0.23, respectively, in the moderately differentiated group, and 2.87+/-0.75, 3.60+/-1.51 and 1.22+/-0.21, respectively, in the poorly differentiated group. Both the ratios and the retention index using 201Tl were significantly lower in the well differentiated group than in the poorly differentiated group. The delayed ratio using 201Tl in the moderately differentiated group was also significantly lower than that in the poorly differentiated group. There were no significant differences in either ratio or the retention index among the three groups using 99Tcm-MIBI. 201Tl SPET is superior to 99Tcm-MIBI SPET for the grading of histopathological differentiation of primary lung adenocarcinoma.