Noninvasive identification of left ventricular involvements in arrhythmogenic right ventricular dysplasia: Comparison of123I-MIBG,201TlCl, magnetic resonance imaging and ultrafast computed tomography

We examined the feasibility of myocardial¹²³I-MIBG,²⁰¹TlCl, magnetic resonance imaging (MRI) and ultrafast computed tomography (UFCT) for the early detection of left ventricular involvements in 15 patients with arrhythmogenic right ventricular dysplasia (ARVD). Radionuclide ventriculography (RNV) and myocardial imaging with¹²³I-MIBG,²⁰¹TlCl, MRI and UFCT were performed in all 15 patients and in 10 normal subjects. The patients’ scans were visually interpreted by two nuclear medicine physicians taking into consideration the extent score (ES) and severity score (SS) calculated by using the bull’s-eye view in relation to normal data derived from the normal subjects. The left ventricular ejection fraction (LVEF) was measured by RNV. Fourteen (93%) patients showed regional¹²³I-MIBG defects, while 12 (80%) patients showed regional²⁰¹TlCl defects. The ES and SS were higher in¹²³I-MIBG than²⁰¹TlCl (ES: 31.5± 18.5 vs. 17.5+18.2, p < 0.01, SS: 34.8±42.2 vs. 16.9±37.5, p< 0.01). Abnormal UFCT and MRI findings suggesting fatty involvements of the LV myocardium were demonstrated in 7 patients (Group B), while 7 patients showed regional¹²³I-MIBG defects without abnormal UFCT and MRI findings (Group A).¹²³I-MIBG was significantly more sensitive than UFCT and MRI (p< 0.05), although one patient, an exception, showed abnormal UFCT findings for the apex of the LV myocardium without abnormal¹²³I-MIBG and MRI findings. The LVEF, as a measure of LV systolic function, was better preserved in Group A than in Group B (59.3±3.6 vs. 45.8±5.8, p< 0.01). The present findings indicated that myocardial imaging with¹²³I-MIBG sensitively detects myocardial damage in patients with ARVD in the early stage when cardiac systolic function is still preserved.     

Use of <Superscript>123</Superscript>I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using ¹²³I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39±57 months, range 1–168 months) with DCM and left ventricular dysfunction underwent ¹²³I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20–75 MBq of ¹²³I-MIBG. Cardiac neuronal uptake of ¹²³I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%±49% vs 162%±26%, P<0.0001, and LVEF=43%±17% vs 26%±11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality.     

Quantitation of myocardial iodine-123 MIBG uptake in SPET studies: a new approach using the left ventricular cavity and a blood sample as a reference

In patients with chronic heart failure increased sympathetic activity is related to unfavourable prognosis. Since myocardial iodine-123 metaiodobenzylguanidine ([¹²³I]MIBG) uptake is related to myocardial noradrenaline content, i.e. cardiac sympathetic activity, measurement of myocardial [¹²³I]MIBG uptake may be of clinical use in determining prognosis or the effect of pharmacological intervention in these patients. The aim of the present study was to evaluate a new method to quantitate myocardial [¹²³I]MIBG uptake with respect to reproducibility and accuracy. Eighteen [¹²³I]MIBG planar and single-photon emission tomography (SPET) studies of patients with chronic heart failure were evaluated. Myocardial uptake was calculated from the myocardial (MYO) to left ventricular cavity (C) count density ratio and the¹²³I activity in a blood sample. This was performed employing planar LAO images, a single-slice SPET method using the midventricular myocardial short-axis slice, and finally a multi-slice SPET method analysing semi-automatically drawn volumes of interest (VOIs). The accuracy of the multi-slice SPET method was verified using a cardiac phantom. The planar method was found to be reproducible [intra- and interobserver coefficients of variation (IACV and IRCV) were 0.025 and 0.012 respectively] but the mean MYO/C count density ratio was only 1.31±0.16 as a consequence of overprojection. For the single-slice SPET method IACV was 0.2 and IRCV was 0.13, representing poor reproducibility. For the multi-slice SPET method IACV was 0.051, IRCV was 0.047 and the mean MYO/C count density ratio was 5.4±2.42. Accuracy was 81% at a true MYO/C count density ratio of 6 in the phantom. It is concluded that the multi-slice SPET method using the left ventricular cavity VOI and a blood sample as a reference is a reproducible and accurate method for assessing myocardial [¹²³I]MIBG uptake.     

Myocardial uptake of meta-[123I]-iodobenzylguanidine ([123I]-MIBG) in patients with myocardial infarct

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.     

Serial change of iodine-123 metaiodobenzylguanidine (MIBG) myocardial concentration in patients with dilated cardiomyopathy

Serial change of the metaiodobenzylguanidine iodine-123 (¹²³I-MIBG) myocardial concentration was investigated in patients with dilated cardiomyopathy (DCM). Eight DCM patients and 6 control subjects were examined. After the injection of thallium-201 and ¹²³I-MIBG, planar chest images were obtained simultaneously for both tracers in every 30–60 min over 5 h. Serial changes of myocardial uptake ratio (MUR) were compared for both tracers. In DCM, the initial MUR of ¹²³I-MIBG did not differ significantly from that of the controls. The washout of ¹²³I-MIBG from the myocardium, however, was significantly increased in DCM. In particular, the decrease in the early phase (15–45 min) was significantly larger in DCM than in the controls (21.2%±7.5% vs. 5.3%±4.0%, P <0.01), showing a significant negative correlation with the left ventricular ejection fraction (r = –0.72 P < 0.05). For ²⁰¹TI, neither the initial MUR nor the washout rate different significantly between the two. Thus, an early rapid decrease of the ¹²³I-MIBG myocardial concentration might characterize DCM and reflect the severity of this disease. Offprint requests to: K. Yamakado     

Correlation between severity of pulmonary arterial hypertension and 123I-metaiodobenzylguanidine left ventricular imaging.

It remains unclear whether cardiac sympathetic nervous function is disturbed in patients with pulmonary arterial hypertension (PH) and how sympathetic dysfunction is related to PH. METHODS: In this study, (123)I-metaiodobenzylguanidine (MIBG) imaging of the heart, which reveals the sympathetic innervation of the left ventricle, was performed in 7 healthy volunteers without cardiopulmonary disease (control subjects); 55 patients with PH, including 27 with chronic thromboembolic pulmonary hypertension (CTEPH) of major vessels; and 28 patients with primary pulmonary hypertension (PPH). RESULTS: Cardiac (123)I-MIBG uptake, assessed as the heart-to-mediastinum activity ratio (H/M), was significantly lower in the CTEPH and PPH groups compared with that in the control group (P < 0.01). Myocardial MIBG turnover, expressed as the washout rate (WR [%]) from 15 to 240 min, was significantly higher in the CTEPH and PPH groups than that in the control group (P < 0.01). In the PPH group, H/M and WR values of MIBG correlated with the severity of pulmonary hypertension (represented by total pulmonary vascular resistance determined by right heart catheterization), the right ventricular ejection fraction determined by electron beam CT, and other variables but did not correlate well in the CTEPH group. In both groups, patients with H/M > or = 2.0 showed better cumulative survival than did those with H/M < 2.0 (P < 0.05). CONCLUSION: Patients with PH have significant left ventricular myocardial sympathetic nervous alteration. (123)I-MIBG imaging of the heart is useful for assessing the severity of pulmonary hypertension caused by PPH or CTEPH.     

Arrhythmogenic right ventricular dysplasia: MR features

Arrhythmogenic right ventricular dysplasia (ARVD) is a heart disease characterized by a total or partial fat replacement of the myocardium. A total of 30 patients were studied with a suspected diagnosis of ARVD. Clinical criteria used for evaluation of ARVD were: (a) ventricular origin arrhythmias with a left bundle branch block configuration, (b) T-wave inversion in the anterior precordial leads, (c) ventricular kinetic alterations observed using echocardiography and angiography and (d) cardiac failure when there are no pathologies attributable to other heart diseases. All patients had serial EKG and echocardiography tests. One third of patients underwent angiocardiography; 7 of 30 had Holter; 7 of 30 had exercise test just to evaluate the effectiveness of the anti-arrhythmic therapy. All patients underwent MRI examination. The following MRI criteria were used: (a) high-intensity areas indicating the fatty substitution of the myocardium, (b) ectasia of the right ventricular outflow tract, (c) dyskinetic bulges, (d) dilation of the right ventricle and (e) enlargement of the right atrium. The diagnosis of ARVD was classified as highly probable for patients manifesting at least three positive criteria, probable with two positive criteria, dubious with one and negative in the absence of all criteria. Highly probable diagnosis of ARVD was made in 8 patients, probable in 4, dubious in 7 and negative in 11. The MRI technique is very effective in the assessment of ARVD. The MRI criteria may be helpful in the diagnosis of this condition. Received 9 August 1995; Revision received 27 December 1995; Accepted 16 July 1996     

Impact of sympathetic innervation on recurrent life-threatening arrhythmias in the follow-up of patients with idiopathic ventricular fibrillation

Purpose Idiopathic ventricular fibrillation (IVF) is defined as VF in the absence of any identifiable structural or functional cardiac disease. The underlying pathophysiological mechanisms are unknown. This study was performed to investigate the potential impact of sympathetic dysfunction, assessed by ¹²³I-meta-iodo-benzylguanidine scintigraphy (¹²³I-MIBG SPECT), on the long-term prognosis of patients with IVF.Methods ¹²³I-MIBG SPECT was performed in 20 patients (mean age 37±13 years) with IVF. Mean follow-up of patients after study entry was 7.2±1.5 years (range 4.9–10.5 years). Ten patients (five men, five women; mean age 43±12 years; p=NS versus study group) with medullary carcinoma of the thyroid gland served as an age-matched control group.Results Abnormal ¹²³I-MIBG uptake was observed in 13 patients (65%). During follow-up, 18 episodes of VF/fast polymorphic ventricular tachycardias occurred in four IVF patients with abnormal ¹²³I-MIBG uptake whereas only two episodes of monomorphic ventricular tachycardia (and no VF) occurred in a single IVF patient with normal ¹²³I-MIBG uptake.Conclusion Impairment of sympathetic innervation may indicate a higher risk of future recurrent episodes of life-threatening ventricular tachyarrhythmias in patients with IVF. Studies in larger cohorts are required to validate the significance of ¹²³I-MIBG SPECT during the long-term follow-up of these patients.The first two named authors contributed equally to this work.     

Quantification of left ventricular size on exercise thallium-201 single-photon emission tomography

The purposes of this study were to determine whether quantification of the left ventricular size on exercise thallium-201 single-photon emission tomography (SPET) correlates with echocardiographic measurements, whether the quantification reflects the severity of coronary artery disease, and whether it can provide supplementary information regarding the severity of coronary artery disease. In 42 control subjects and 110 patients who underwent coronary angiography, we performed exercise²⁰¹Tl SPET and quantified six non-regional markers: lung²⁰¹Tl uptake on an initial planar image (Lung/Heart), left ventricular width on a tomogram (Width), change in the Width from the initial to delayed tomograms (Width), count ratio of the left ventricular cavity to the myocardium (C/M), count ratio of the lung to the myocardium (UM), and count ratio of the lung to the left ventricular cavity (L/C). In 76 patients, furthermore, the Width was compared with echocardiographic measurements. The Width correlated with echocardiographic measurements (P<0.001). The Width and Width were significantly different among zero-, one-, two- and three-vessel disease (P<0.001). However, the Width and Width could not improve the power of discrimination for multi-vessel disease derived from the Lung/Heart. The six non-regional markers correlated with each other (P<0.001). Among the six markers, the Lung/Heart was only the independent discriminator for multi-vessel disease. In conclusion, quantification of the left ventricular size on exercise²⁰¹Tl SPET correlated with echocardiographic measurements and reflected the severity of coronary artery disease, but may be replaced with quantitation of the lung²⁰¹Tl uptake.     

Iodine-123 metaiodobenzylguanidine in the assessment of late cardiac effects from cancer therapy

Recognition of adverse late cardiac effects from cancer therapy may enable identification of patients with risk of cardiotoxicity upon cancer retreatment. In this study the feasibility of using iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) heart scintigraphy to detect abnormalities of the myocardial adrenergic neurone function in the late period after cancer therapy was evaluated in relation to the left ventricle ejection fraction (LVEF) in 18 cancer patients: 11 had undergone thoracic irradiation involving the heart, in five cases in combination with anthracycline therapy, 11–228 months (median 60 months) before radionuclide tests, while seven had not received previous anthracycline and/or radiotherapy (controls). The¹²³I-MIBG cardiac uptake, expressed as a heart-to-mediastinum ratio on planar images after 4 h, ranged from 1.21 to 1.76 (median 1.56) in cancer therapy patients, which was significantly decreased (P=0.0006) in comparison with controls (range 1.81–2.06, median 1.9). The myocardial¹²³I-MIBG washout, calculated from planar images after 15 min and 4 h, and LVEF also showed significant differences, but with some overlap in individual cases. In cancer therapy patients, cardiac abnormalities seen on planar images and additional single-photon emission tomographic images varied from focal defects to diffusely reduced myocardial uptake. It is concluded that¹²³I-MIBG heart scintigraphy, which is able to identify cardiac adrenergic neurone abnormalities in the follow-up period after cancer therapy, may help to identify relapsed patients who are at increased risk of developing cardiotoxicity during retreatment with cardiotoxic therapy modalities.This paper was presented as an oral communication at the European Association of Nuclear Medicine Congress in Brussels, 1995     

Dipyridamole and exercise SPET provide different estimates of myocardial ischaemic areas: role of the severity of coronary stenoses and of the increase in heart rate during exercise

In patients unable to perform a maximal exercise test, dipyridamole single-photon emission tomography (SPET) has a higher capacity than exercise SPET to detect coronary artery disease (CAD). However, in patients with myocardial ischaemia who are able to perform a maximal exercise test, it is not known whether these two tests may be equally used to assess the areas of myocardial ischaemia. This study was aimed at comparing the results provided by dipyridamole and exercise SPET in CAD patients with documented exercise myocardial ischaemia. Forty CAD patients who had undergone exercise thallium-201 SPET and who had myocardial ischaemia documented by an unequivocally positive exercise test underwent an additional ²⁰¹Tl SPET study after dipyridamole infusion and low-level (40 W) exercise. The extent of defects was compared between the two tests and predictors of discrepant results were sought among data from exercise testing and coronary angiography. The extent of SPET defects was equivalent between the two tests in only 11 patients (28%), larger defects being observed with exercise in 18 [average difference: 12%±5% of left ventricle (LV)] and with dipyridamole in 11 (average difference: 15%±11% of LV). The best independent predictors of discrepancies between the two tests were: (1) increase in heart rate at exercise SPET, with defects being smaller at exercise than after dipyridamole in none of the patients with an increase >60 bpm (0/14), but in 42% of the others (11/26; P=0.004); and (2) an ischaemic territory related to a <70% coronary stenosis, for which SPET defects were always induced at exercise (10/10) but in only 30% (3/10) with dipyridamole (P=0.0004). Exercise and dipyridamole SPET provide different estimates of myocardial ischaemic areas. Dipyridamole allows the unmasking of perfusion abnormalities in patients who have low increases in heart rate at exercise SPET. However, dipyridamole is also much less efficient at inducing perfusion abnormalities in the ischaemic areas supplied by coronary stenoses of intermediate severity at rest angiography. Received 20 January 2000 and in revised form 18 March 2000     

I-MIBG myocardial scintigraphy as a noninvasive screen for the diagnosis of coronary artery spasm

Background. It has been suggested that the sympathetic nervous system might play an important role in the development of coronary artery spasm. However, no cardiac imaging modality has been able to demonstrate abnormal sympathetic innervation in patients with coronary artery spasm. The purpose of this study was to assess the presence and location of abnormal sympathetic innervation using iodine 123-metaiodobenzylguanidine (¹²³I-MIBG) single photon emission computed tomography (SPECT) and to evaluate the clinical efficacy of ¹²³I-MIBG SPECT as a noninvasive screening test in patients with coronary artery spasm.Methods and Results. Coronary arteriography and a provocative test with intravenous administration of ergonovine maleate were performed in 26 patients (20 men, 6 women, mean age 48.2 ± 12.0 years, range 20 to 67 years) who were suspected of having a coronary artery spasm. The subjects were divided into 2 groups: group 1 (n = 18) comprised subjects with a positive provocative test result, and group 2 (n = 8) comprised subjects with negative provocative test results. Ten healthy subjects served as controls. No abnormal MIBG uptake was observed in the control subjects. Abnormal sympathetic nervous innervation using ¹²³I-MIBG SPECT was observed either as a reduced uptake or a defective pattern in the perfused areas in 13 of the 18 regions supplied by vessels of ergonovine-induced vasospasm. Normal sympathetic innervation, as evidenced by normal ¹²³I-MIBG uptake, was noted in all of the 60 segments of normal vessel territories. Reduced uptake of ¹²³I-MIBG was not detected in the perfused areas of 5 vasospasm-induced vessels (perfusion territory of left anterior descending coronary artery [LAD] and the right coronary artery [RCA] in 2 and 3 patients, respectively). The sensitivity and specificity of ¹²³I-MIBG for detection of coronary artery spasm were 72.2% (95% confidence interval [CI] 55 % to 89 %) and 100 %, respectively. The positive predictive and negative predictive values were 100% and 92.3% (95% CI 91% to 93%), respectively.Conclusion. ¹²³I-MIBG SPECT is a feasible method to evaluate noninvasively and localize the territories of coronary arteries with spasm. Invasive diagnostic coronary arteriography with ergonovine provocation test may be unnecessary for diagnosis of coronary artery spasm in patients with typical resting pain, negative exercise test or normal thallium perfusion scan results, but showing abnormalities in ¹²³I-MIBG SPECT.     

Sequential scintigraphic strategy for the differentiation of brain tumours

Both thallium-201 and iodine-123 α-methyltyrosine (¹²³I-IMT) have been shown to be useful in the diagnostic evaluation of brain tumours. The aim of this study was to investigate the respective contributions of ²⁰¹Tl and ¹²³I-IMT single-photon emission tomography (SPET) in the non-invasive evaluation of intracerebral tumours. We analysed 65 patients with the following brain tumours: 8 non-neoplastic lesions, 4 meningiomas, 12 low-grade gliomas, 28 high-grade gliomas, 11 metastases and 2 high-grade lymphomas. ²⁰¹Tl SPET and ¹²³I-IMT SPET were performed [start of ²⁰¹Tl SPET: 15 min p.i. (early) and 180 min p.i. (delayed); start of ¹²³I-IMT SPET: 15 min p.i.]. The intensity of uptake was quantified as the ratio between tracer accumulation in the tumour and in the contralateral hemisphere. None of the non-neoplastic lesions or low-grade gliomas expressed marked ²⁰¹Tl uptake. All malignant tumours except one small metastasis and all meningiomas except one small, cystic and degenerated lesion showed significant ²⁰¹Tl accumulation [Tl(15’)>2.0]; ¹²³I-IMT uptake was either absent or intermediate in non-malignant lesions except in two low-grade gliomas; the highest levels were observed in high-grade gliomas followed by metastases and lymphomas (mean IMT: 2.7 vs 2.1 vs 1.8), with metastases showing a high variability in ¹²³I-IMT uptake (range: 0.8–3.6). Using ²⁰¹Tl to distinguish non-neoplastic lesions from malignant tumours and meningiomas, 63 of 65 patients were characterised correctly. In the latter group, high-grade gliomas were correctly identified in 27 of 28 cases by their amino acid uptake. It is concluded that the combination of ²⁰¹Tl and ¹²³I-IMT surpasses the accuracy of each single test in the differentiation of space-occupying lesions of the brain. Based on these preliminary results, a sequential strategy is proposed involving an initial ²⁰¹Tl SPET study and an additional ¹²³I-IMT SPET study in the event of positive ²⁰¹Tl uptake. Received 1 October 1999 and in revised form 8 January 2000     

Evaluation of cardiac sympathetic neuronal integrity in diabetic patients using iodine-123 metaiodobenzylguanidine

Autonomic dysfunction is associated with increased mortality in diabetic patients. To evaluate the cardiac autonomic dysfunction in these patients, a prospective study was undertaken using iodine-123 metaiodobenzylguanidine (MIBG) single-photon emission tomography (SPET). The study groups consisted of ten diabetic patients with cardiac autonomic neuropathy (group 1) and six without autonomic neuropathy (group II). Autonomic nervous function tests, thallium scan, radionuclide ventriculographic data including ejection fraction and wall motion study, and 24-h urine catecholamine levels were evaluated.¹²³I-MIBG SPET was performed at 30 min and 4 h following injection of 3 mCi of¹²³I-MIBG in groups I and II and in normal subjects (n=4). On planar images, the heart to mediastinum (H/M) ratio was measured. Defect pattern and severity of MIBG uptake were qualitatively analysed on SPET. Compared with control subjects, diabetic patients had a reduced H/M ratio regardless of the presence of clinical autonomic neuropathy. There was no difference in H/M ratio between groups I and II. On SPET images, focal or diffuse defects were demonstrated in all patients in group I, and in five of the six patients in group II. The extent of defects tended to be more pronounced in group I than in group II. In conclusion, SU1-MIBG scan was found to be a more sensitive method than clinical autonomic nervous function tests for the detection of autonomic neuropathy in diabetes.     

123I-MIBG myocardial scintigraphy as a noninvasive screen for the diagnosis of coronary artery spasm

Background  It has been suggested that the sympathetic nervous system might play an important role in the development of coronary artery spasm. However, no cardiac imaging modality has been able to demonstrate abnormal sympathetic innervation in patients with coronary artery spasm. The purpose of this study was to assess the presence and location of abnormal sympathetic innervation using iodine 123-metaiodobenzylguanidine (¹²³I-MIBG) single photon emission computed tomography (SPECT) and to evaluate the clinical efficacy of ¹²³I-MIBG SPECT as a noninvasive screening test in patients with coronary artery spasm. Methods and Results  Coronary arteriography and a provocative test with intravenous administration of ergonovine maleate were performed in 26 patients (20 men, 6 women, mean age 48.2±12.0 years, range 20 to 67 years) who were suspected of having a coronary artery spasm. The subjects were divided into 2 groups: group 1 (n=18) comprised subjects with negative provocative provocative test result, and group 2 (n=8) comprised subjects with negative provocative test results. Ten healthy subjects served as controls. No abnormal MIBG uptake was observed in the control subjects. Abnormal sympathetic nervous innervation using ¹²³I-MIBG SPECT was observed either as a reduced uptake or a defective pattern in the perfused areas in 13 of the 18 regions supplied by vessels of ergonovine-induced vasospasm. Normal sympathetic innervation, as evidenced by normal ¹²³I-MIBG uptake, was noted in all of the 60 segments of normal vessel territories. Reduced uptake of ¹²³I-MIBG was not detected in the perfused areas of 5 vasospasm-induced vessels (perfusion territory of left anterior descending coronary artery [LAD] and the right coronary artery [RCA] in 2 and 3 patients, respectively). The sensitivity and specificity of ¹²³I-MIBG for detection of coronary artery spasm were 72.2% (95% confidence interval, [CI] 55% to 89%) and 100%, respectively. The positive predictive and negative predictive values were 100% and 92.3% (95% CI 91% to 93%), respectively. Conclusion   ¹²³I-MIBG SPECT is a feasible method to evaluate noninvasively and localize the territories of coronary arteries with spasm. Invasive diagnostic coronary arteriography with ergonovine provocation test may be unnecessary for diagnosis of coronary artery spasm in patients with typical resting pain, negative exercise test or normal thallium perfusion scan results, but showing abnormalities in ¹²³I-MIBG SPECT. Presented in part at the European Association of Nuclear Medicine Congress, September 1996, Copenhagen, Denmark.     

Improved labelling of no-carrier-added 123I-MIBG and preliminary clinical evaluation in patients with ventricular arrhythmias.

Meta-[123I]iodobenzylguanidine (123I-MIBG) is currently used to assess myocardial sympathetic innervation by single photon emission tomography (SPET). In recent studies, an enhanced cardiac uptake of 123I-MIBG with high specific activity has been reported, suggesting the clinical potential of no-carrier-added (n.c.a.) 123I-MIBG in the assessment of abnormalities in cardiac sympathetic function. This paper describes the preparation of n.c.a. 123I-MIBG by non-isotopic Cu(I)-assisted [123I]iododebromination and by [123I]iododestannylation, both resulting in n.c.a. 123I-MIBG with radiochemical yields of 88 +/- 6% and high specific activity (> or = 6.3 TBq.mumol-1) in a total synthesis time of less than 50 min. The diagnostic potential of n.c.a. 123I-MIBG (> 6.3 TBq.mumol-1) was studied in 13 patients (nine patients with malignant ventricular arrhythmias and four patients suspected of phaeochromocytoma) and compared to commercial 123I-MIBG (approximately 75 MBq.mumol-1) using a dual-headed SPET camera (MULTISPECT II). High specific activity results in higher 123I-MIBG uptake in the heart and in the liver in all patients. The calculated heart-to-lung and heart-to-liver count ratios 4.5 h post-injection increased by 22 +/- 6% and 10 +/- 5% with n.c.a. 123I-MIBG compared to commercial 123I-MIBG respectively. In contrast, no significant correlation between the specific activity of 123I-MIBG and lung uptake could be established in this study. Analysis of radioactivity in blood after the intravenous injection of n.c.a. and commercially available 123I-MIBG showed an initial rapid clearance of radioactivity from blood, followed by a plateau from 60 min onwards. Within the first 24 h, more than 85% of the plasma activity was unchanged 123I-MIBG. The free 123I-iodide concentration determined 24 h post-injection was 2 +/- 1% with commercial 123I-MIBG and 3 +/- 2% with n.c.a. 123I-MIBG. In conclusion, the results of this investigation indicate that n.c.a. 123I-MIBG is a promising clinical tool for imaging myocardial sympathetic dysfunction by SPET. High specific activity n.c.a. 123I-MIBG can now be prepared by simple one-step methods giving high radiochemical yields and high purity suitable for clinical application. This encourages the further clinical validation of n.c.a. 123I-MIBG on a large scale.     

Doxorubicin-induced cardiac neurotoxicity: Study with iodine 123-labeled metaiodobenzylguanidine scintigraphy

Background

Iodine 123-labeled metaiodobenzylguanidine (¹²³I-MIBG) can be used to generate a scintigraphic image of the adrenergic nervous innervation of the heart.

Methods and Results

To test the hypothesis that doxorubicin may lead to damage of cardiac neurons, we examined 37 patients with various malignant neoplasms, 14 of whom were on therapy with doxorubicin. All patients were examined with ¹²³I-MIBG scintigraphy and radionuclide ventriculography. Cardiac ¹²³I-MIBG uptake was assessed by means of a heart to mediastinum activity ratio (H/M). Left ventricular ejection fraction was not different in patients with or without doxorubicin. In patients receiving doxorubicin, the H/M ratio was significantly lower (1.73±0.25 vs 2.13±0.25, p<0.001) and correlated with doxorubicin cumulative dose (r=?0.51, p<0.001). By using a H/M ratio of 1.73 as a cutoff point, ¹²³I-MIBG uptake was abnormal in none of the 23 patients not receiving and 6 of 14 patients receiving doxorubicin therapy (p<0.001). In 10 patients initially not receiving doxorubicin, ¹²³I-MIBG scintigraphy was repeated after receiving 236±47 mg/m² of doxorubicin. The H/M became abnormal in 3 of 10 patients, whereas the ejection fraction became abnormal in 2 of 10 patients.

Conclusion

¹²³I-MIBG cardiac uptake decreases in a doxorubicin dose-dependent way, indicating a cardiac adrenergic neurotoxic effect of doxorubicin. This phenomenon appears early and generally before deterioration of the ejection fraction.     

Clinical value of triple-energy window scatter correction in simultaneous dual-isotope single-photon emission tomography with123I-BMIPP and201TI

To improve the image quality in simultaneous dual-isotope single-photon emission tomography (SPET) with iodine-123 labelled 15-(p-iodophenyl)-3-methylpentadecanoic acid (BMIPP) and thallium-201, we applied the triple-energy window method JEW) for correction of the cross-talk and scatter artifact. Seventy-one patients with coronary artery disease were included.²⁰¹T1 cross-talk into the¹²³I acquisition window (group 1,n = 30) and¹²³I cross-talk into the²⁰¹Tl window (group 2,n = 41) were studied. In group 1,¹²³I images were first obtained (single-isotope images), followed by²⁰¹Tl injection and SPET acquisition using dual-isotope windows (dual-isotope images). In group 2, the order was reversed. The dual-isotope SPET images with and without TEW were compared with the single-isotope images. Qualitative evaluation was performed by scoring the segmental defect pattern. Detectability of the mismatched fatty acid metabolism on dual-isotope SPET was evaluated by receiver operating characteristic (ROC) curve analysis. Segmental defect pattern agreement between dual and corrected single images was significantly improved by TEW correction (P<0.01). The agreement was particularly improved in segments with absence of uptake. There was no significant difference between TEW-corrected dual-isotope SPET and corresponding single-isotope SPET with regard to either % defect count or background activity. Mismatched fatty acid metabolism depicted by dual-isotope SPET predicted abnormal wall motion more accurately with TEW than without TEW. With TEW, a practical method for scatter and cross-talk correction in clinical settings, simultaneous dual¹²³I-BMIPP/²⁰¹Tl SPET is feasible for the assessment of myocardial perfusion/metabolism mismatch.     

Correlation between cardiac norepinephrine overflow during exercise and cardiac 123I-MIBG uptake in patients with chronic heart failure.

Cardiac (123)I-metaiodobenzylguanidine ((123)I-MIBG) uptake is reduced in chronic heart failure, and its reduction is reported to relate to the decrease in exercise capacity. Reduced (123)I-MIBG uptake may predict an inadequately reduced adrenergic drive to the heart during cardiac sympathetic stimulation, including exercise. However, there is little information about the relationship between cardiac (123)I-MIBG uptake at rest and norepinephrine (NE) release during exercise in relation to the exercise capacity in the failing heart. The aim of this study was to examine whether cardiac (123)I-MIBG uptake at rest can predict cardiac sympathetic activity during exercise in patients with chronic heart failure. We determined how cardiac (123)I-MIBG uptake at rest relates to NE overflow from the heart during symptom-limited graded exercise in such patients. METHODS: Twelve patients (mean +/- SD, 52 +/- 12 y) with chronic stable heart failure performed symptom-limited graded exercise tests under catheterizations with a 4-min stage using a supine bicycle ergometer within 2 wk after (123)I-MIBG imaging. NE concentrations in the arterial and coronary sinus blood (NE(A) and NE(CS), respectively) were measured at each exercise stage, and NE overflow was approximated by the difference between NE(CS) and NE(A) (NE(CS-A)). RESULTS: The left ventricular ejection fraction at rest was 47% +/- 16% and peak oxygen uptake was 17.7 +/- 5.1 mL/kg/min. The heart-to-mediastinum uptake ratio of the delayed (123)I-MIBG image (1.00 - 1.72; mean +/- SD, 1.30 +/- 0.19) correlated with NE(CS-A) at peak exercise (r = 0.80, P < 0.01) and peak heart rate (r = 0.73, P < 0.01) but not with peak oxygen uptake. CONCLUSION: Cardiac (123)I-MIBG uptake of the delayed image can predict the degree of the increase in adrenergic drive to the heart during sympathetic stimuli induced by exercise in patients with chronic heart failure.     

Prediction of left ventricular dilatation with thallium-201 SPET imaging after primary angioplasty in patients with acute myocardial infarction

Progressive ventricular dilatation is an important prognostic factor in patients with acute myocardial infarction. We evaluated clinical, angiographic, echocardiographic and thallium-201 single-photon emission tomography (SPET) imaging variables predictive of the change in left ventricular volume during a 7-month follow-up period after primary angioplasty in patients with acute myocardial infarction. Thirty-six patients with first acute myocardial infarction treated with primary angioplasty within 12 h of onset underwent 201Tl SPET imaging (5.8+/-2.1 days after angioplasty). Changes in left ventricular volume were assessed over the 7-month period. The left ventricle dilated significantly after angioplasty ( P<0.001). Multivariate analysis revealed that the number of segments with 201Tl uptake <40% of peak activity was a single independent predictor of increase in end-diastolic volume index between 1 week and 7 months ( R2=0.41, P< 0.001). The presence of two or more segments with 201Tl uptake <40% predicted an increase in end-diastolic volume index of > or =6 ml/m2 with positive and negative predictive values of 85% (17/20) and 75% (12/16), respectively. It is concluded that, following primary angioplasty in patients with acute myocardial infarction, the extent of myocardial infarction assessed by 201Tl SPET can identify those who will develop ventricular dilatation during the subsequent 7 months.