Long-term recovery of left ventricular function after primary angioplasty for acute myocardial infarction.

AIMS: To investigate changes in left ventricular function in the first 6 months after acute myocardial infarction treated with primary angioplasty. To assess clinical variables, associated with recovery of left ventricular function after acute myocardial infarction. METHODS: Changes in left ventricular function were studied in 600 consecutive patients with acute myocardial infarction, all treated with primary angioplasty. Left ventricular ejection fraction was measured by radionuclide ventriculography in survivors at day 4 and after 6 months. Patients with a recurrent myocardial infarction within the 6 months were excluded. RESULTS: Successful reperfusion (TIMI 3 flow) by primary angioplasty was achieved in 89% of patients. The mean ejection fraction at discharge was 43.7%+/-11.4, whereas the mean ejection fraction after 6 months was 46.3%+/-11.5 (P<0.01). During the 6 months, the mean relative improvement in left ventricular ejection fraction was 6%. An improvement in left ventricular function was observed in 48% of the patients; 25% of the patients had a decrease, whereas in the remaining patients there was no change. After univariate and multivariate analysis, an anterior infarction location, an ejection fraction at discharge < or =40% and single-vessel disease were significant predictors of left ventricular improvement during the 6 months. CONCLUSIONS: After acute myocardial infarction treated with primary angioplasty there was a significant recovery of left ventricular function during the first 6 months after the infarction. An anterior myocardial infarction, single-vessel coronary artery disease, and an initially depressed left ventricular function were independently associated with recovery of left ventricular function. Multivessel disease was associated with absence of functional recovery. Additional studies, investigating complete revascularization are needed, as this approach may potentially improve long-term left ventricular function.

Prognostic importance of left ventricular function after angioplasty or thrombolysis for acute myocardial infarction.

OBJECTIVES: To compare long-term clinical outcome after acute myocardial infarction treated with primary coronary angioplasty or thrombolytic therapy, and to study the determinants of survival. BACKGROUND: Primary coronary angioplasty results in a higher patency rate and a better short-term survival when compared with thrombolytic therapy, but so far limited information has been available regarding long-term clinical outcome. METHODS: Patients with acute myocardial infarction (n=395) were randomised to treatment with either intravenous streptokinase or primary angioplasty, and were followed for up to eight years. RESULTS: A total of 105 patients died, 42 patients in the primary coronary angioplasty group compared with 63 patients in the streptokinase group (p=0.03). Death and nonfatal reinfarction occurred in 53 patients in the angioplasty group, compared with 94 patients in the streptokinase group (p<0.001). The major cause of long-term mortality is sudden death. Multivariate analysis showed that left ventricular function was the most important predictor for both total mortality and sudden death. CONCLUSION: The benefits of primary coronary angioplasty compared with streptokinase are well sustained during long-term follow-up.

Clinical characteristics and outcome of patients with acute myocardial infarction and preinfarction angina.

OBJECTIVES/BACKGROUND: Preinfarction angina is associated with reduced myocardial infarct size in patients treated with thrombolysis. Our objective was to assess the relation between preinfarction angina and infarct size, left ventricular function and clinical outcome in patients treated with primary angioplasty (PTCA) and compare this with patients treated with thrombolysis. METHODS: In the Zwolle Infarction Study, 953 patients were treated for acute myocardial infarction between 1990 and 1996; 761 patients underwent primary PTCA and 192 patients received thrombolysis as reperfusion therapy. RESULTS: Preinfarction angina was present in about 50% of the patients, who were categorised into angina ≤24 hours and angina >24 hours before infarction. Patients in both treatment groups have a longer ischaemic time when preinfarction angina is present. In patients treated with thrombolysis, preinfarction angina ≤24 hours results in a smaller enzymatic infarct. Thrombolysis seems to be more effective when preinfarction angina occurs within the 24 hours prior to myocardial infarction. Collateral filling of the infarct-related artery is more often seen in patients with preinfarction angina. In the primary PTCA group, a longer ischaemic time in patients with preinfarction angina does not result in increased infarct size, and this effect remains after excluding patients with collateral filling. CONCLUSIONS: The protective effect of preinfarction angina is likely to be due to better collateral filling of the infarct-related artery and to ischaemic preconditioning of the myocardium.

Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction.

BACKGROUND: As compared with thrombolytic therapy, primary coronary angioplasty results in a higher rate of patency of the infarct-related coronary artery, lower rates of stroke and reinfarction, and higher in-hospital or 30-day survival rates. However, the comparative long-term efficacy of these two approaches has not been carefully studied. METHODS: We randomly assigned a total of 395 patients with acute myocardial infarction to treatment with angioplasty or intravenous streptokinase. Clinical information was collected for a mean (+/-SD) of 5+/-2 years, and medical charges associated with the two treatments were compared. RESULTS: A total of 194 patients were assigned to undergo primary angioplasty, and 201 to receive streptokinase. Mortality was 13 percent in the angioplasty group, as compared with 24 percent in the streptokinase group (relative risk, 0.54; 95 percent confidence interval, 0.36 to 0.87). Nonfatal reinfarction occurred in 6 percent and 22 percent of the two groups, respectively (relative risk, 0.27; 95 percent confidence interval, 0.15 to 0.52). The combined incidence of death and nonfatal reinfarction was also lower among patients assigned to angioplasty than among those assigned to streptokinase, with a relative risk of 0.13 (95 percent confidence interval, 0.05 to 0.37) for early events (within the first 30 days) and a relative risk of 0.62 (95 percent confidence interval, 0.43 to 0.91) for late events (after 30 days). The rates of readmission for heart failure and ischemia were also lower among patients in the angioplasty group than among patients in the streptokinase group. Total medical charges per patient were lower in the angioplasty group (16,090 dollars) than in the streptokinase group (16,813 dollars, P=0.05). CONCLUSIONS: During five years of follow-up, primary coronary angioplasty for acute myocardial infarction was associated with lower rates of early and late death and nonfatal reinfarction, fewer hospital readmissions for ischemia or heart failure, and lower total medical charges than treatment with intravenous streptokinase.

[Prevalence of asymptomatic cardiac ischemia in men with diabetes mellitus type I]. / Prevalentie van asymptomatische cardiale ischemie bij mannen met diabetes mellitus type I.

OBJECTIVE: To establish the prevalence of 'silent ischaemia' of the myocardium in male patients with type 1 diabetes mellitus using a non-invasive cardiac examination, and to determine what clinical variables are related to silent ischaemia. DESIGN: Prospective, cross-sectional. METHOD: Males aged 20-69 years who visited the outpatient department of Internal Medicine of the De Weezenlanden Hospital in Zwolle between 1 February 1992 and 31 January 1995, and who showed no symptoms of ischaemic cardiopathy (angina pectoris, myocardial infarction or arrhythmias) or of chronic obstructive pulmonary disease, were examined for cardiac ischaemia by means of a 24-hour Holter registration and a perfusion scintigram after administration of dipyridamol. In order to demonstrate a possible connection between cardiovascular risk factors and silent ischaemia, the patients with an abnormal and those with a normal scintigram were compared by means of multivariate analysis. RESULTS: Data were collected on 92 successive patients, with a median age of 40 years (range 22-69). There were 19 patients (21%) with an abnormal myocardial scintigram. On average they were older and had a longer history of diabetes mellitus. An abnormal Holter registration was observed in 14 patients (15%), abnormality of either the Holter registration or the myocardial scintigram in 28 patients (30%) and abnormality of both the myocardial scintigram and the Holter registration in 5 patients (5%). The duration of the diabetes mellitus, and a diastolic blood pressure > or = 90 mm Hg were statistically significant and independent predictors of an abnormal myocardial scintigram (relative risks 1.08 and 3.4 per year, respectively). CONCLUSIONS: The prevalence of cardiac ischaemia in males with type 1 diabetes mellitus without cardiac symptoms is approximately 20%. Abnormal test results were associated with a longer duration of the diabetes mellitus and a diastolic blood pressure > or = 90 mm Hg.

Prognostic value of predischarge radionuclide ventriculography at rest and exercise after acute myocardial infarction treated with thrombolytic therapy or primary coronary angioplasty. The Zwolle Myocardial Infarction Study Group.

BACKGROUND: Previous studies have demonstrated the prognostic value of radionuclide ventriculography at rest and exercise in patients post myocardial infarction (MI). The number of studies in patients treated with modern reperfusion techniques, including thrombolysis or primary angioplasty, however, is limited. HYPOTHESIS: The aim of this study was to evaluate the prognostic significance of predischarge radionuclide ventriculography at rest and exercise in patients with acute MI treated with thrombolysis or primary angioplasty. METHODS: A total of 272 consecutive patients with acute MI who were randomized to thrombolysis or primary coronary angioplasty underwent predischarge resting and exercise radionuclide ventriculography. Left ventricular ejection fraction at rest, decrease in ejection fraction during exercise > 5 units below the resting value, angina pectoris, ST-segment depression, and exercise test ineligibility were related to subsequent cardiac events (cardiac death, nonfatal reinfarction) during follow-up. RESULTS: During a mean follow-up of 30 +/- 10 months, cardiac death occurred in 11 (4%) patients and nonfatal reinfarction in 14 (5%) patients. Resting left ventricular ejection fraction was the major risk factor for cardiac death. In patients with an ejection fraction < 40%, cardiac death occurred in 16% compared with 2% in those with an ejection fraction > or = 40% (p = 0.0004). In addition, cardiac death tended to be higher in patients ineligible than in those eligible for exercise testing (11 vs. 3%, p = 0.08). None of the other exercise variables (decrease in ejection fraction during exercise > 5 units below the resting value, angina pectoris or ST-segment depression) were predictive for cardiac death. When all exercise test variables in each patient were combined and expressed as a risk score, a low risk (n = 185) and a higher risk (n = 87) group of patients could be identified, with cardiac death occurring in 1 and 10%, respectively. As the predictive accuracy of a negative test was high, radionuclide ventriculography was of particular value in identifying patients at low risk for cardiac death. Radionuclide ventriculography was not able to predict recurrent nonfatal MI. CONCLUSION: In patients with MI treated with thrombolysis or primary angioplasty, radionuclide ventriculography may be helpful in identifying patients at low risk for subsequent cardiac death. In this respect, left ventricular ejection fraction at rest was the major determinant. Variables reflecting residual myocardial ischemia were of limited prognostic value. Identification of a large number of patients at low risk allows selective use of medical resources during follow-up in this subgroup and has significant implications for the cost effectiveness of reperfusion therapies.

Comparison of radionuclide angiography with three echocardiographic parameters of left ventricular function in patients after myocardial infarction.

AIMS: Left ventricular function is an important outcome measure in patients with coronary artery disease, in particular in patients after myocardial infarction. It is reliably assessed by radionuclide angiography, but echocardiographic wall motion scoring might be an attractive alternative. METHODS: Four days after reperfusion therapy for acute myocardial infarction both radionuclide angiography and echocardiography were performed in 90 patients. Segmental wall motion scoring (WMSI) and visual estimation of the left ventricular ejection fraction (LVEF) was done by 2 independent observers. Repeated analysis was performed 1 month after the first reading. In 41 patients the LVEF was assessed quantitatively by tracing of endocardial outlines of the left ventricle. RESULTS: Both correlation with radionuclide angiography (estimated LVEF: r = 0.71, WMSI: r = -0.68, Tracing: r = 0.59) and inter- and intra-observer variability (estimated LVEF: 19% and 15%, WMSI: 65% and 59%) were in favour of the LVEF estimation method. Correlation with radionuclide angiography measurements was related to the quality of the echocardiogram and to the extent of coronary artery disease. CONCLUSION: Simple echocardiographic estimation of left ventricular ejection fraction in patients after reperfusion therapy for acute myocardial infarction proved to be superior to quantitative assessment of ejection fraction and to segmental wall motion scoring in comparison with radionuclide angiography.

Randomized comparison of primary coronary angioplasty with thrombolytic therapy in low risk patients with acute myocardial infarction.

OBJECTIVES: We sought to compare primary coronary angioplasty and thrombolysis as treatment for low risk patients with an acute myocardial infarction. BACKGROUND: Primary coronary angioplasty is the most effective reperfusion therapy for patients with acute myocardial infarction; however, intravenous thrombolysis is easier to apply, more widely available and possibly more appropriate in low risk patients. METHODS: We stratified 240 patients with acute myocardial infarction at admission according to risk. Low risk patients (n = 95) were randomized to primary angioplasty or thrombolytic therapy. The primary end point was death, nonfatal stroke or reinfarction during 6 months of follow-up. Left ventricular ejection fraction and medical charges were secondary end points. High risk patients (n = 145) were treated with primary angioplasty. RESULTS: In low risk patients, the incidence of the primary clinical end point (4% vs. 20%, p < 0.02) was lower in the group with primary coronary angioplasty than in the group with thrombolysis, because of a higher rate of reinfarction in the latter group. Mortality and stroke rates were low in both treatment groups. There were no differences in left ventricular ejection fraction or total medical charges. High risk patients had a 14% incidence rate of the primary clinical end point. CONCLUSIONS: Simple clinical data can be used to risk-stratify patients during the initial admission for myocardial infarction. Even in low risk patients, primary coronary angioplasty results in a better clinical outcome at 6 months than does thrombolysis and does not increase total medical charges.

Mortality, reinfarction, left ventricular ejection fraction and costs following reperfusion therapies for acute myocardial infarction.

The comparative efficacy of thrombolytic drugs and primary angioplasty for acute myocardial infarction have recently been studied, but long-term follow-up data have not yet been reported. We conducted a randomized trial involving 301 patients with acute myocardial infarction; 152 patients were randomized to primary angioplasty and 149 to intravenous streptokinase. Left ventricular function was assessed with a radionuclide technique both at hospital discharge and at the end of the follow-up period. Follow-up data were collected after a mean (+/-SD) of 31 +/- 9 months. Total medical costs were calculated. At the end of the follow-up period, 5% of the angioplasty patients had died from a cardiac cause compared to 11% of the patients randomized to intravenous streptokinase, P = 0.031. Cardiac death or a non-fatal reinfarction occurred in 7% of angioplasty patients compared to 28% of streptokinase patients, P < 0.001. There was a sustained benefit of angioplasty compared to streptokinase on left ventricular function. The total medical costs in the two groups were similar. Coronary anatomy (patency and single or multivessel disease), infarct location and previous myocardial infarction were important determinants of clinical outcome and costs. After 31 +/- 9 months of follow-up, primary angioplasty compared to intravenous streptokinase results in a lower rate of cardiac death and reinfarction, a better left ventricular ejection fraction, and no increase in total medical costs.

Limitation of infarct size and preservation of left ventricular function after primary coronary angioplasty compared with intravenous streptokinase in acute myocardial infarction.

BACKGROUND: Early and effective flow through the infarct-related vessel is probably of paramount importance for limitation of infarct size and preservation of left ventricular function in patients with acute myocardial infarction. Primary coronary angioplasty may offer advantages in these respects compared with thrombolytic therapy. The purpose of the present study was to assess the effects on estimated enzymatic infarct size and left ventricular function in patients with acute myocardial infarction randomly assigned to undergo primary angioplasty or to receive intravenous streptokinase. METHODS AND RESULTS: We evaluated 301 patients with signs of acute myocardial infarction and without contraindications for thrombolysis who presented within 6 hours after onset of symptoms or between 6 and 24 hours if there was evidence of ongoing ischemia. One hundred fifty-two patients were randomly assigned to undergo primary angioplasty, and 149 patients were assigned to receive treatment with streptokinase (1.5 million U i.v.). Infarct size was estimated from enzyme release. Global left ventricular ejection fraction and regional wall motion, if possible in combination with exercise testing, were evaluated by radionuclide ventriculography before discharge. Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 through the infarct-related vessel within 120 minutes after admission was achieved in 92% of all patients assigned to receive primary angioplasty therapy. Myocardial infarct size was 23% smaller in the angioplasty group compared with patients assigned to receive streptokinase (1003 +/- 784 versus 1310 +/- 1198 U/L, P = .012). Global left ventricular ejection fraction (50 +/- 9% versus 45 +/- 11%, P < .001) and regional wall motion in the infarct-related zones (42 +/- 14% versus 34 +/- 13%, P < .001) were better in the angioplasty group, which could mainly be contributed to myocardial salvage in the infarct-related areas. The observed differences were more pronounced in patients with an anterior wall myocardial infarction, although patients with a nonanterior infarct location also showed a beneficial effect of primary coronary angioplasty on left ventricular function compared with streptokinase therapy. Furthermore, the observed differences appeared to be more pronounced in patients presenting relatively early (within 2 hours) after onset of symptoms. CONCLUSIONS: In patients with acute myocardial infarction, primary angioplasty results in a smaller infarct size and a better preserved myocardial function compared with patients randomized to receive treatment with intravenous streptokinase. This is probably due to early and optimal blood flow through the infarct-related vessel, as can be accomplished in a very high percentage of patients undergoing primary coronary angioplasty.

Immediate coronary angioplasty versus intravenous streptokinase in acute myocardial infarction: left ventricular ejection fraction, hospital mortality and reinfarction.

OBJECTIVES: The purpose of the present study was to compare intravenous streptokinase therapy with immediate coronary angioplasty without antecedent thrombolytic therapy with regard to left ventricular function and hospital mortality and reinfarction. BACKGROUND: Despite the widespread use of intravenous thrombolytic therapy and immediate percutaneous transluminal coronary angioplasty, these two strategies to treat patients with an acute myocardial infarction have only recently been compared in randomized trials. Coronary angioplasty has been shown to result in a higher patency rate of the infarct-related coronary artery, with a less severe residual stenotic lesion, compared with streptokinase therapy, but whether this more favorable coronary anatomy results in clinical benefit remains to be established. METHODS: We studied 301 patients with acute myocardial infarction randomly assigned to undergo immediate coronary angioplasty without antecedent thrombolytic therapy or to receive intravenous streptokinase therapy. Before discharge left ventricular ejection fraction was measured by radionuclide scanning. RESULTS: The in-hospital mortality rate in the streptokinase group was 7% (11 of 149 patients) compared with 2% (3 of 152 patients) in the angioplasty group (p = 0.024). In the streptokinase group recurrent myocardial infarction occurred in 15 patients (10%) versus in 2 (1%) in the angioplasty group (p < 0.001). Either death or nonfatal reinfarction occurred in 23 patients (15%) in the streptokinase group and in 5 patients (3%) in the angioplasty group (p = 0.001). Left ventricular ejection fraction was 44 +/- 11% (mean +/- SD) in the streptokinase group versus 50 +/- 11% in the angioplasty group (p < 0.001). CONCLUSIONS: These findings indicate that immediate coronary angioplasty without antecedent thrombolytic therapy results in better left ventricular function and lower risk of death and recurrent myocardial infarction than treatment with intravenous streptokinase.

A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction.

BACKGROUND: Despite the widespread use of intravenous thrombolytic therapy and of immediate percutaneous transluminal coronary angioplasty for the treatment of acute myocardial infarction, randomized comparisons of the two approaches to reperfusion are lacking. We report the results of a prospective, randomized trial comparing immediate coronary angioplasty (without previous thrombolytic therapy) with intravenous streptokinase treatment. METHODS: A total of 142 patients with acute myocardial infarction were randomly assigned to receive one of the two treatments. The left ventricular ejection fraction was measured by radionuclide scanning before hospital discharge. Quantitative coronary angiography was performed to assess the degree of residual stenosis in the infarct-related arteries. RESULTS: A total of 72 patients were assigned to receive streptokinase and 70 patients to undergo immediate angioplasty. Angioplasty was technically successful in 64 of the 65 patients who underwent the procedure. Infarction recurred in nine patients assigned to receive streptokinase, but in none of those assigned to receive angioplasty (P = 0.003). Fourteen patients in the streptokinase group had unstable angina after their infarction, but only four in the angioplasty group (P = 0.02). The mean (+/- SD) left ventricular ejection fraction as measured before discharge was 45 +/- 12 percent in the streptokinase group and 51 +/- 11 percent in the angioplasty group (P = 0.004). The infarct-related artery was patent in 68 percent of the patients in the streptokinase group and 91 percent of those in the angioplasty group (P = 0.001). Quantitative coronary angiography revealed stenosis of 36 +/- 20 percent of the luminal diameter in the angioplasty group, as compared with 76 +/- 19 percent in the streptokinase group (P < 0.001). CONCLUSIONS: Immediate angioplasty after acute myocardial infarction was associated with a higher rate of patency of the infarct-related artery, a less severe residual stenotic lesion, better left ventricular function, and less recurrent myocardial ischemia and infarction than was intravenous streptokinase.

4-[123I]iodospiperone as a ligand for dopamine DA receptors: in vitro and in vivo experiments in a rat model.

Radioiodinated spiperone is of interest for dopamine (DA) receptor studies in the living human brain by single photon emission computed tomography (SPECT). Stimulated by data obtained with [11C]-N-methyl-spiperone we synthesized 4-[123I]iodospiperone and investigated the in vitro binding characteristics of this ligand to the striatal membrane of the rat and the in vivo distribution over various rat brain regions. The in vitro binding experiments showed that this radioligand displays about 10 times less affinity for the DA receptor than spiperone and specific binding, as shown with [3H]spiperone, was not observed. Displacement by butaclamol was not observed. The in vivo studies demonstrated that both 4-[123I]iodospiperone and [3H]spiperone concentrate in striatal tissue, respectively, 1.9 and 3.5 times as high as in cerebellar tissue. Haloperidol pretreatment largely prevented this accumulation. In view of the obtained target-to-non-target ratios we believe, however, that this accumulation in brain areas rich in DA-receptors does not offer prospects for clinical receptor imaging with SPECT.

Functional brain imaging with I123-amphetamine. First experience in the Netherlands.

Single Photon Emission Computed Tomography (SPECT) has been used in the last five years as a method for cerebral bloodflow imaging, especially in cerebral infarction. In this study the first experiences in the Netherlands are presented. In 57.6% of our patients lesions, defined by SPECT were larger than those found by CT. This was not only seen in patients with cerebral infarction but also in hematoma. In 33.3% the size of the lesions were comparable. In 10 out of 14 patients with a solitary lesion in one hemisphere a decreased perfusion was seen in the contralateral cerebellar hemisphere. This phenomenon is called crossed cerebellar diaschisis. One patient with probably Alzheimer disease, showing a specific flow pattern, is discussed.

Cyclotron isotopes and radiopharmaceuticals--XXXIII. Synthesis and structural effect of selective biliary excretion of halogenated indotricarbocyanines.

Five indotricarbocyanines of structure I were synthesized and labeled with 131I in the 5 position. The substituent, R, was varied [formula: see text] R = H, F, Cl, Br and I. The dynamics of hepatic uptake and blood clearance of the labeled compounds were determined in mice. Kidney uptake in all cases was negligible. The hepatic excretion displayed 2 components. The initial hepatic disappearance rates of R = H and R = F were 7.3 and 4.5%/min, respectively. The maximum liver activity in mice occurred at 2--5 min and the % remaining in the liver at 0.5 h was 3.6, 8.6, 19, 29 and 47% for R = H, F, Cl, Br and I substitution. It is notable that a small change in the substituent at the 5' position in the molecule has such a pronounced effect. Whether electronic and/or steric effects are controlling the mechanism of hepatobiliary clearance is not obvious. A correlation of the liver activity with the covalent radius of R was noted. The comparative studies were at an injected dose of 0.4--0.6 mumol/kg, and typically at a specific activity of 200 mCi/mol. Loading dose effects were not appreciable under these conditions. Scintigraphic results are reported for dogs and a rabbit. The results suggest that indotricarbocyanines of structure (I) labeled with 123I or with 18F are potential radiopharmaceuticals for dynamic hepatobiliary function studies.

Estrogen receptor binding radiopharmaceuticals: II. Tissue distribution of 17 alpha-methylestradiol in normal and tumor-bearing rats.

Tritiated 17 alpha-methylestradiol was synthesized to investigate the potential of the carbon-11-labeled analog as an estrogen-receptor-binding radiopharmaceutical. In vitro, 17 alpha-methylestradiol is bound with high affinity to the cytoplasmic estrogen receptor from rabbit uterus (Kd = 1.96 x 10(-10)M), and it sediments as an 8S hormone-receptor complex in sucrose gradients. The compound shows specific uptake in the uterus of the adult rat, within 1 hr after injection. After 30 min the uterine uptake was 1.73% dose/g. In female rats bearing DMBA-induced tumors, specific uterine and tumor uptakes were observed, although at 30 min the tumor uptake was only 23-30% of the uptake in the uterus. Tritiated 17 alpha-methylestradiol with a specific activity of 6 Ci/mmole showed a similar tissue distribution. Our results indicate that 17 alpha-methylestradiol is promising as an estrogen-receptor-binding radiopharmaceutical.

Radiotracers binding to estrogen receptors: I: Tissue distribution of 17 alpha-ethynylestradiol and moxestrol in normal and tumor-bearing rats.

Ethynylestradiol and moxestrol can be labeled with carbon-11 by introducing this positron emitter in the 17 alpha-ethynyl group. To investigate their potential as radiotracers binding to estrogen receptors, we studied the tissue distribution of tritiated ethynylestradiol and moxestrol, with specific activities of 57 Ci/mmol and 77-90 Ci/mmol, respectively, in the adult female rat. At 30 min after injection, both compounds showed specific uptake in the uterus (% dose/g): 2.52 for ethynylestradiol and of 2.43 for moxestrol. A decrease of the specific activity to 6-9 Ci/mmol resulted in uterine uptakes of 1.60 and 2.10 respectively, for ethynylestradiol and moxestrol, at 30 min. In the female rat bearing DMBA-induced mammary tumors, specific uptake was also measured in the tumors, although the values were only 25-30% of the uterine uptake. Moxestrol showed a greater uptake selectivity in the tumors compared with ethynylestradiol. From this study we conclude that ethynylestradiol and moxestrol have good potential as tracers binding to mammary tumors that contain estrogen receptors.

Rapid decarboxylation of carbon-11 labelled DL-DOPA in the brain: a potential approach for external detection of nervous structures.

The cerebral distribution of the positron-emitting agent [1-11C]beta-(3,4-dihydroxyphenyl)-D,L-alpha-alanine ([11C]DOPA) was studied after intravenous injection in rats pretreated with the peripheral decarboxylase inhibitor, carbidopa. Within 15 min of injection the accumulation of carbon-11 was almost twice as high in cortical areas and cerebellum as in the striatum and the brain stem. After destruction of catecholamine-containing nerve endings with 6-hydroxydopamine, the level of carbon-11 in the striatum was higher than in rats not treated with this neurotoxin. Pretreatment of rats with haloperidol or L-DOPA did not change the distribution pattern of carbon-11. Without pretreatment with carbidopa a uniform distribution of the label in the brain was observed. We suggest that [11C]DOPA is a potentially useful agent for external detection with positron imaging systems in patients and large animals of brain regions rich in the enzyme dopa-decarboxylase. (EC 4.1.1.26).