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Radioiodine is currently used routinely in the treatment of hyperthyroidism including Graves’ disease (GD), toxic multinodular goitre (TMNG) and toxic solitary nodule (TSN) but no consensus exists on the most appropriate way to prescribe iodine – fixed dose or calculated doses based on the gland size or turnover of 131I. We carried out the first nationwide French survey assessing the current practices in radioiodine treatment of hyperthyroidism.

Introduction:– The invasive quantification of coronary flow reserve (CFR), the index of microcirculatory resistance (IMR), and fractional flow reserve (FFR) allows to assess coronary physiology. Although semi-conductor (CZT) SPECT myocardial perfusion reserve (MPR) has been previously compared with FFR, there are no data documenting the relationships between CZT SPECT MPR on one hand and CFR and/or IMR on the other hand. We assessed the performances of noninvasive CZT SPECT MPR in comparison with invasively determined FFR, CFR, and IMR.Methods:– Rest and dipyridamole-induced stress myocardial blood flow and MPR were quantified using 99mTc-SestaMIBI and a Discovery NM 530c camera in 26 patients with suspected or known coronary artery disease who underwent conventional invasive coronary angiography. Thermodilution-derived resting and adenosine-induced hyperemic mean transit times, distal intracoronary pressures, and mean aortic pressures were assessed for the quantification of FFR, CFR, and IMR values.Results:– Only 2/35 vessels presented with a pathological (<0.8) FFR. A moderate yet significant correlation was observed between regional CZT SPECT MPR and CFR (r=0.40, P=.02). The sensitivity, specificity, positive and negative predictive value, and accuracy of regional CZT SPECT MPR vsCFR were 69% [44-86%], 94% [74-100%], 91% [65-100%], 77% [56-90%], and 82% [65-93%], respectively. In territories without underlying CAD (n=32), CZT SPECT MPR values were significantly higher in those with CFR≥2 and IMR<25 (negative composite criterion, n=14) than in those with CFR<2 and IMR≥25 (positive composite criterion, n=8, CZT SPECT MPR, 2.6 [2.1-3.6] vs1.6 [1.2-1.8]), P<.01). Regional CZT SPECT MPR displayed sensitivity, specificity, positive and negative predictive value, and accuracy of 87% [53-99%], 100% [78-100%], 100% [64-100%], 93% [70-99%], and 95% [77-99%] for the diagnosis of a positive composite criterion, respectively.Conclusions:– CZT SPECT MPR presented a moderate, significant correlation with thermodilution CFR and good diagnostic performances for the detection of patients at high risk of cardiovascular events (low CFR and high IMR) in the absence of obstructive CAD.

Background: Technetium 99m N-NOET is a new myocardial perfusion imaging agent currently in phase III clinical trials in Europe. In vitro studies on newborn rat cardiomyocytes have shown that calcium inhibitors, such as verapamil or diltiazem, inhibit its cellular uptake by 40%. To determine whether such a specificity exists ex vivo, we studied the effect of verapamil, diltiazem, and nifedipine on the myocardial uptake and retention of Tc-99m N-NOET in isolated perfused rat hearts. Methods and Results: After a 15-minute baseline period, rat hearts were perfused with 0.5 μmol/L verapamil (n=6), 0.75 μmol/L diltiazem (n=6), or 0.1 μmol/L nifedipine (n=6) for 10 minutes before the injection of a bolus (40 μCi/250 μL) of the tracer. Control hearts were perfused with either 1.5 mmol/L calcium (same concentration as in the treated groups; n=7) or 0.75 mmol/L calcium (same contractility as in the treated groups; n=6). Myocardial activity of Tc-99m N-NOET was monitored for 30 minutes. The functional parameters of the hearts were recorded throughout the experiments. References: Calcium inhibitors induced a 40% to 55% decrease in maximal first derivative of left ventricular pressure (dP/dt) (0.0001&lt;P&lt;.001 versus control, calcium 1.5 mmol/L). After 30 minutes, tracer retention was 51.6%±6.1% injected dose (ID)/g and 54.2%±10.2% ID/g for control hearts perfused with 1.5 mmol/L and 0.75 mmol/L calcium, respectively (P=not significant). Myocardial activity of Tc-99m N-NOET was not modified in hearts perfused with verapamil (50.0%±4.1% ID/g), diltiazem (47.2%±8.7% ID/g), or nifedipine (51.7%±3.4% ID/g; P=not significant versus control hearts perfused with 1.5 mmol/L or 0.75 mmol/L calcium). Conclusions: Verapamil, diltiazem, and nifedipine were not responsible for any variations in Tc-99m N-NOET uptake and retention in the isolated rat-heart model. This might be explained by the binding of the tracer to endothelial cells, which do not present voltage-dependent calcium channels.

blocking properties, were synthesized. The first route chosen, from 4-aminophenol and the chloroformate β7, had to be abandoned because of the formation of the oxazolidinone 10 during the epoxidation step. The aminoalcohol 17 prepared from the practolol 1 finally gave the target compounds by condensation with the iodoallylic chloroformates 8 (E + Z). The secondary Boc-protected amine function was regenerated without removing the carbamate function situated in the p-postion, by using mild reaction conditions (1 N HCl).

Abstract.: Considering the current need to improve cost-effectiveness in cancer patient management, a prospective study was undertaken in order to define the optimal combination of bone scan and tumour marker assays in breast and lung cancer strategies, as has been done in the case of prostate cancer. All patients with breast or lung cancer referred to the Nuclear Medicine Department of the Grenoble Teaching Hospital between December 1995 and April 1997 were included. A blood sample was drawn in each case for marker assay (CA15-3 or CEA and CYFRA 21-1) on the same day as the bone scan. Two hundred and seventy-five patients were included: 118 with lung cancer and 157 with breast cancer. With regard to lung cancer, no information useful for guiding bone scan prescription was obtained through CEA and CYFRA 21-1 assays. For breast cancer, the results suggest that in asymptomatic patients, a CA15-3 level of less than 25 U/ml (upper normal value chosen as the threshold) is strongly predictive of a negative bone scan; by contrast, high tumour marker levels are predictive of neoplastic bone involvement. When a doubtful bone scan is obtained in a patient with breast cancer, a normal marker level makes it highly probable that bone scan abnormalities are not related to malignancy.

Abstract.: β-Methyl-substituted free fatty acids (FFAs) have been developed for myocardial single-photon emission tomography (SPET) imaging, but little is known about their kinetics in ischaemic conditions. The aim of this study was to determine the changes in the myocardial kinetics of a β-methyl-branched FFA, [123I]16-iodo-3-methyl-hexadecanoic acid (MIHA), under ischaemic conditions. The kinetics of MIHA were analysed: (a) using a blood-perfused isolated heart model subjected to moderate ischaemia (50% flow reduction) and (b) in patients who had an exercise thallium-201 SPET defect corresponding to either necrotic (n = 13) or chronically ischaemic and viable (n = 15) myocardium, and who underwent two consecutive SPET studies after MIHA injection. In animals, the myocardial early retention fraction of MIHA, but not its clearance rate, was dependent on coronary flow, the early retention fraction being higher in ischaemic than in normoxic conditions (0.24±0.10 vs 0.14±0.04, P = 0.004). In the patient SPET studies, the uptake of MIHA calculated in ischaemic and viable areas (G1: 74%±9% of maximal left ventricular value) was different from that calculated in necrotic (G2: 59%±7%, P<0.001) or normal (G3: 88±6%, P<0.001) areas. By contrast, MIHA-clearance calculated between the two consecutive SPET studies was not different in G1, G2 and G3. Unlike in the case of other FFAs, the myocardial clearance of MIHA is not decreased by ischaemia. However, the early retention of MIHA is increased in the case of a moderate reduction in coronary flow, a property which might help in the detection of viability in chronically ischaemic myocardium.

Abstract: The best test presently available to ascertain residual viability within an infarct-related area involves the use of fluorine-18 fluorodeoxyglucose (FDG) to detect the persistence of some cellular metabolism. Rest reinjection of thallium-201 is a less accurate alternative but is easy to perform. Iodinated fatty acids, which are used with standard gamma cameras, are proposed as markers of cellular metabolism. This study was performed to assess the value of 16-iodo-3-methyl-hexadecanoic acid (MIHA) as a marker of the residual cellular metabolism by comparison with FDG in patients with a recent myocardial infarction, and to evaluate its contribution compared with the201Tl stress-redistribution-reinjection technique. Stress-redistribution-reinjection201T1 imaging, rest MIHA imaging and glucoseloaded FDG imaging were performed in 22 patients with recent myocardial infarction. Out of the 628 myocardial segments obtained from the left ventricular analysis, 400 were hypoperfused (relative uptake <0.75 of maximum uptake on stress201T1 imaging), 177 of which were severely hypoperfused (relative uptake <0.50). Receiver operating characteristic (ROC) curves for predicting metabolic myocardial viability with FDG were derived from the results in respect of (a)201T1 activity during exercise, redistribution and reinjection and (b) MIHA up-take, using the two FDG thresholds most commonly considered to define metabolic viability (0.50 and 0.60). Analysis of the 400 hypoperfused segments demonstrated that201T1 reinjection was the most accurate test in predicting the presence of myocardial viability (area under the ROI curves=0.85 and 0.86 at the 0.50 and 0.60 FDG thresholds, respectively;P<0.05 vs other tests). The global predictive values of MIHA and201T1 reinjection were, respectively, 0.87 and 0.89 at the 0.50 FDG threshold (NS), and 0.82 and 0.87 at the 0.60 FDG threshold (NS). When only the 177 severely hypoperfused segments were considered,201T1 reinjection remained the most accurate test (accuracy 0.84 at the 0.50 FDG threshold and 0.82 at the 0.60 FDG threshold), while the accuracy of MIHA decreased significantly (0.78 at the 0.50 FDG threshold and 0.73 at the 0.60 FDG threshold,P<0.05 vs201T1 reinjection). In all circumstances, MIHA was less specific than201T1 reinjection for the detection of metabolic viability. In conclusion, in patients with recent myocardial infarction, MIHA accurately detects the persistence of metabolic viability, but is not superior to201T1.

Objectives. This study was designed to assess the prognostic value of thallium-201 single-photon emission computed tomographic (thallium SPECT) perfusion imaging in patients evaluated for stable angina pectoris and to examine the relation, if any, between the preface and extent of myocardial defect and future fatal or nonfatal cardiovascular events (revascularization, secondary myocardial infarction).

Metaiodobenzylguanidine (MIBG), an analogue of noradrenaline, is used to explore the functional integrity of sympathetic nerve endings in the human heart. Various drugs inhibit noradrenaline transport systems and may block the uptake of MIBG. As in vivo studies of the effect of these drugs on myocardial [123I]MIBG uptake are often difficult to perform, we used an in vitro human blood platelet model for this purpose. A platelet preparation from healthy volunteers was incubated with [125I]MIBG alone or different concentrations of drugs currently used in cardiology. Labetalol and propranolol inhibited [125I]MIBG uptake, whereas all other drugs tested (other ß-blockers, calcium inhibitors, digoxin and amiodarone) had no effect even at doses exceeding 50 µM. The labetalol dose inhibiting 50% of [125I]MIBG uptake was lower than the plasma concentration of this drug in treated patients, whereas the propranolol dose was higher. This in vitro study of the effect of drugs on MIBG uptake by human blood platelets is predictive of their in vivo effect on myocardial uptake of [123I]MIBG in treated patients, provided that plasma concentration is taken into account.

Sleep has a specific physiology with related cardiovascular changes. We have previously found in respiratory patients [chronic obstructive pulmonary disease (COPD) and sleep apnea syndrome (OSAS)] an unexpected decrease in left ventricular ejection fraction (LVEF) at waking in the morning when compared with the rest period during the day. Whether this observation was linked to the consequences of the respiratory abnormalities or reflected physiological fluctuations related to the changes in autonomic nervous system tone remained unknown. Thus, we have set out to analyze the changes in LVEF with sleep in normal individuals. Eight healthy young men had LVEF measured before and after submaximal exercise, at rest before bedtime, and on waking in the morning. Technetium-99m with in vivo red cell labelling was used. Sleep parameters were assessed using classical polysomnography. In order to detect any influence of autonomic nervous system stimulation on LVEF, sympathovagal tone (SVT) was also assessed during night-time LVEF measurements using spectral analysis of RR intervals. LVEF at rest was within the normal limits for all the subjects (range 51-62%). On submaximal exercise, the LVEF increased in four subjects, was unchanged in two, and decreased in two. The main result concerns the changes in LVEF overnight. In the morning, LVEF decreased dramatically in three subjects and reached a level of <30% in four. These decreases in LVEF were not related to changes in SVT or sleep structure. LVEF values returned to normal in 30 min. The LVEF changes during exercise are in accordance with previous data in the literature. The dramatic decrease in LVEF observed in the morning could be related either to vascular resistance changes or to nocturnal variations in cardiac contractility, which both need further studies to be established.

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono ß) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono ß into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.

Meta-123I-iodobenzylguanidine (123I-MIBG), which is an analog of norepinephine, can be used to evaluate the integrity and function of sympathetic nerve endings in the heart. Myocardial uptake of 123I-MIBG was studied in 30 myocardial infarction patients and compared with the distribution of blood flow assessed with 201Tl. It was found that when a cold defect appeared on the 201Tl scintigram, its localization was identical to the cold defect on the 123I-MIBG scintigram. On the other hand, in three cases, a defect was found on the 123I-MIBG scintigram, corresponding to the electrocardiographic localization of the infarct, whereas the 201Tl scintigram was normal. Most strikingly, the present study shows that drugs (antagonists of the adrenergic receptors, calcium antagonists, amiodarone) decrease or even abolish (as in the case of labetalol) myocardial uptake of 123I-MIBG. Consequently, any interpretation of the 123I-MIBG scintigram must take into account the treatment administered.

The present study was designed to prospectively evaluate whether reinjection mallium-201 single-photon emission computed tomography (SPECT) has a significant additive predictive value for occurrence of perioperative cardiac events in clinically selected patients at high cardiac risk undergoing abdominal aortic surgery. Of a group of 517 consecutive patients referred, 134 had ≥2 of the following clinical or electrocardiographic cardiac risk variables: age >70 years; history of myocardial infarction, angina, or congestive heart failure; diabetes mellitus; hypertension with severe left ventricular hypertrophy; and Q waves or ischemic ST-segment abnormalities on electrocardiogram at rest. Operation was performed after thallium SPECT study. Twelve patients (9%) had major perioperative events (cardiac death or nonfatal myocardial infarction) and 18 patients had other cardiac events (unstable angina, congestive heart failure, or severe ventricular tachyarrhythmia). Variables correlated with the occurrence of major events were history of myocardial infarction (p < 0.05) and the presence (p < 0.001) and number of segments with thallium reversible defects (p < 0.001). In multivariate analysis, history of myocardial infarction (p < 0.05) and the number of segments with reversible thallium defects (p < 0.001) were independent predictors. When all the cardiac events were taken into consideration, all the previous variables, as well as Q waves and ischemic ST abnormalities on the electrocardiogram, showed significant predictive value in both univariate and multivariate analyses. Furthermore, thallium SPECT imaging has an additive predictive value for major cardiac events over clinical and electrocardiographic risk factors. When performed on clinically selected patients at high cardiac risk undergoing abdominal aortic surgery, thallium SPECT demonstrates significant prognostic value for cardiac events over that provided by clinical variables alone.

Objectives. We compared the ability of rest single-photon emission computed tomography (SPECT) with [123I]-16-iodo-3-methylhexadecanoic acid (MIHA) and the thallium-201 (Tl-201) rest-reinjection technique to detect myocardial viability after infarction.

Aims Positron emission tomography–computed tomography (PET-CT) is a highly sensitive clinical molecular imaging modality to study atherosclerotic plaque biology. Therefore, we sought to develop a new PET tracer, targeting vascular cell adhesion molecule (VCAM)-1 and validate it in a murine atherosclerotic model as a potential agent to detect atherosclerotic plaque inflammation. Methods and results The anti-VCAM-1 nanobody (Nb) (cAbVCAM-1–5) was radiolabelled with Fluorine-18 (18F), with a radiochemical purity of >98%. In vitro cell-binding studies showed specific binding of the tracer to VCAM-1 expressing cells. In vivo PET/CT imaging of ApoE−/− mice fed a Western diet or control mice was performed at 2h30 post-injection of [18F]-FB-cAbVCAM-1–5 or 18F-control Nb. Additionally, plaque uptake in different aorta segments was evaluated ex vivo based on extent of atherosclerosis. Atherosclerotic lesions in the aortic arch of ApoE−/− mice, injected with [18F]-FB-anti-VCAM-1 Nb, were successfully identified using PET/CT imaging, while background signal was observed in the control groups. These results were confirmed by ex vivo analyses where uptake of [18F]-FB-cAbVCAM-1–5 in atherosclerotic lesions was significantly higher compared with control groups. Moreover, uptake increased with the increasing extent of atherosclerosis (Score 0: 0.68 ± 0.10, Score 1: 1.18 ± 0.36, Score 2: 1.49 ± 0.37, Score 3: 1.48 ± 0.38%ID/g, Spearman's r2 = 0.675, P < 0.0001). High lesion-to-heart, lesion-to-blood, and lesion-to-control vessel ratios were obtained (12.4 ± 0.4, 3.3 ± 0.4, and 3.1 ± 0.6, respectively). Conclusion The [18F]-FB-anti-VCAM-1 Nb, cross-reactive for both mouse and human VCAM-1, allows non-invasive PET/CT imaging of VCAM-1 expression in atherosclerotic plaques in a murine model and may represent an attractive tool for imaging vulnerable atherosclerotic plaques in patients.

To investigate the effect of amlodipine on baroreflex sensitivity and sympathetic system activity, 36 patients with essential hypertension were randomized to once-daily, double-blind treatment with amlodipine 5 mg or placebo 5 mg for 60 days. Measurements with a Finapres device allowed calculation of baroreflex sensitivity and blood pressure (BP) variability. Adrenergic activity was assessed via measurements of lymphocyte ß2-adrenoceptors and plasma catecholamine concentrations. Compared with placebo, amlodipine significantly decreased BP, but did not significantly alter baroreflex sensitivity. Spectral analysis of Finapres data showed that, compared with placebo, amlodipine decreased the variability of systolic blood pressure, diastolic blood pressure, and RR interval in the low frequency band. There were no simultaneous changes in adrenergic function, however, suggesting that these effects of amlodipine were not mediated via sympathetic nervous system activation. Am J Hypertens 2001;14:424–428 © 2001 American Journal of Hypertension, Ltd.

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