123I-MIBG Uptake Research Articles

Impaired Lung 123I-MIBG Uptake on SPECT in Pulmonary Emphysema

The aim of this study was to evaluate impaired lung uptake of (123)I-metaiodobenzylguanidine ((123)I-MIBG) on SPECT, compared with perfusion SPECT and morphologic CT, in patients with pulmonary emphysema (PE). (123)I-MIBG SPECT was performed at 15 min and 4 h after intravenous injection of (123)I-MIBG in 36 PE patients with a history of smoking and variable-extent low-attenuation areas on CT, indicative of emphysematous changes, and in 16 controls with no history of smoking and no noticeable low-attenuation areas. The distribution of (123)I-MIBG was compared with that of low-attenuation areas on CT and perfusion on SPECT at the base of the 180 lung lobes of the PE patients. Total-lung (123)I-MIBG kinetics were calculated, including early and delayed lung-to-mediastinum uptake ratios and washout rate. The controls showed a fairly uniform lung (123)I-MIBG distribution nearly consistent with perfusion. PE patients had heterogeneous (123)I-MIBG defects showing frequent discordance with low-attenuation areas or perfusion distribution; (123)I-MIBG defects were more extensive than low-attenuation areas in 76 lobes (42.2%) of 31 patients (86%) and more extensive than perfusion defects in 44 lobes (24.4%) of 22 patients (61%). (123)I-MIBG defects were seen regardless of the absence of noticeable low-attenuation areas and perfusion defects in 19 lobes (10.5%) of 16 patients (44%). All total-lung (123)I-MIBG kinetic parameters in PE patients were significantly lower than the control values (P < 0.0001), with significant correlation with alveolar-arterial oxygen tension gradient but without correlation with the extent of perfusion defects or low-attenuation areas. (123)I-MIBG SPECT allows evaluation of lung pathophysiology in PE independently of perfusion SPECT or morphologic CT, and impairment of lung (123)I-MIBG uptake may be more extensive than perfusion or morphologic abnormalities in PE.

Systemic blood pressure profile correlates with cardiac 123I-MIBG uptake in patients with Parkinson's disease

To examine the correlation between the systemic blood pressure profile and cardiac 123I-metaiodobenzylguanidine (MIBG) uptake in patients with Parkinson's disease (PD), we monitored circadian blood pressure patterns of 37 PD patients of 49 to 85years of age (mean, 71.8±8.4years) using a portable blood pressure monitoring device. The duration of PD was 0.5 to 15years, and the disability level (modified Hoehn and Yahr stage) ranged from 1.0 to 4.0 (mean, 2.7±0.7). There were 37 age- and sex-matched control subjects. Cardiac MIBG scintigraphy was performed for the 37 PD patients. Based on the nocturnal fall in mean arterial blood pressure (MABP), we classified patients into extreme dippers (nocturnal reduction of MABP >20%), dippers (>10% but <20%), nondippers (<10% but >0%), and inverted dippers (<0%). Average 24-hour MABP values revealed reduced BP variability in PD patients. The percentage nocturnal fall in MABP was significantly different between PD patients and control subjects (p<0.05). Significant correlations were found between % MABP reduction and the heart-to-mediastinum (H/M) ratio on early and delayed images (p<0.01). The UPDR motor score, early and delay H/M ratios were also significantly different between patients who were and were not dippers (p<0.05). The present results reported for the first time a significant correlation between the systemic blood pressure profile and cardiac 123I-MIBG uptake in patients with PD. The degeneration between the brainstem and the postganglionic neurons of myocardial sympathetic nerves may progress in parallel in patients with PD.

123I-MIBG scintigraphy/SPECT versus 18F-FDG PET in paediatric neuroblastoma

To analyse different uptake patterns in (123)I-MIBG scintigraphy/SPECT imaging and (18)F-FDG PET in paediatric neuroblastoma patients. We compared 23 (123)I-MIBG scintigraphy scans and 23 (18)F-FDG PET scans (mean interval 10 days) in 19 patients with a suspected neuroblastic tumour (16 neuroblastoma, 1 ganglioneuroblastoma, 1 ganglioneuroma and 1 opsomyoclonus syndrome). SPECT images of the abdomen or other tumour-affected regions were available in all patients. Indications for (18)F-FDG PET were a (123)I-MIBG-negative tumour, a discrepancy in (123)I-MIBG uptake compared to the morphological imaging or imaging results inconsistent with clinical findings. A lesion was found by (123)I-MIBG scintigraphy and/or (18)F-FDG PET and/or morphological imaging. A total of 58 suspicious lesions (mean lesion diameter 3.8 cm) were evaluated and 18 were confirmed by histology and 40 by clinical follow-up. The sensitivities of (123)I-MIBG scintigraphy and (18)F-FDG PET were 50% and 78% and the specificities were 75% and 92%, respectively. False-positive results (three (123)I-MIBG scintigraphy, one (18)F-FDG PET) were due to physiological uptake or posttherapy changes. False-negative results (23 (123)I-MIBG scintigraphy, 10 (18)F-FDG PET) were due to low uptake and small lesion size. Combined (123)I-MIBG scintigraphy/(18)F-FDG PET imaging showed the highest sensitivity of 85%. In 34 lesions the (123)I-MIBG scintigraphy and morphological imaging findings were discrepant. (18)F-FDG PET correctly identified 32 of the discrepant findings. Two bone/bone marrow metastases were missed by (18)F-FDG PET. (123)I-MIBG scintigraphy and (18)F-FDG PET showed noticeable differences in their uptake patterns. (18)F-FDG PET was more sensitive and specific for the detection of neuroblastoma lesions. Our findings suggest that a (18)F-FDG PET scan may be useful in the event of discrepant or inconclusive findings on (123)I-MIBG scintigraphy/SPECT and morphological imaging.

The prognostic value of semi-quantitative 123I mIBG scintigraphy at diagnosis in high-risk neuroblastoma: Validation of the SIOPEN score method.

9511 Background: A semi-quantitative reporting method developed by an international expert panel (J Nucl Med 2009;50:1379) was used to evaluate the role ofI-123 meta-IodoBenzylGuanidine [123I mIBG] imaging in high risk neuroblastoma [HR-NBL]. Method: Patterns of skeletal 123I mIBG uptake were assignednumerical scores (Mscore) ranging from 0 (no metastasis) to 72 (diffuse metastases) within 12 body areas as described previously (J Nucl Med 2009;50:1379). 271 anonymised, paired image data sets acquired at diagnosis and on completion of Rapid COJEC induction chemotherapy were reviewed, constituting a representative sample of 1602 children treated prospectively within the HR-NBL1/SIOPEN trial. Pre-and post-treatment Mscores were compared with bone marrow cytology (BM) and 3 year event free survival (EFS). Results: 224/271 patients showed skeletal mIBG uptake at diagnosis and were evaluable for mIBG response. Complete skeletal mIBG response (CR) to Rapid COJEC induction was achieved by 66%, 34% and 15% of pati...

Follow‐up study of cardiac 123I‐MIBG scintigraphy in idiopathic REM sleep behavior disorder

Cardiac (123) I-metaiodobenzylguanidine ((123) I-MIBG) uptake in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is markedly reduced, as in Parkinson's disease (PD). We performed (123) I-MIBG scintigrams on patients with iRBD and PD. After the initial (123) I-MIBG scintigram, we retested subjects after a mean of 2.8 years. The delayed heart-to-mediastinum (H/M) ratio of cardiac (123) I-MIBG uptake was not significantly reduced between the first and second study in either group (P = 0.050, P = 0.091, respectively). Follow-up imaging revealed a mean decline of 4.21 ± 9.06% or 6.40 ± 19.02% in the delayed H/M ratio in those with iRBD or PD, respectively. The (123) I-MIBG uptake findings might indicate progression early in the course of iRBD or PD, but the progression is heterogeneous and independent of development of motor symptoms.

Extra-adrenal Pheochromocytoma in the Organ of Zuckerkandl: Diagnosis and Treatment Strategies

Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare catecholamine-secreting neuroendocrine tumors arising from chromaffin tissue and can occur within the adrenal medulla (PHEO) or extra-adrenal sites (PGL). The most common site for PGL is the organ of Zuckerkandl, extra-adrenal chromaffin tissue near the origin of the inferior mesenteric artery.We here present 2 patients with extra-adrenal PGL in the organ of Zuckerkandl, located by iodine-123-metaiodobenzylguanadine ( (123)I-MIBG) scintigraphy and thereafter treated surgically or with iodine-131-metaiodobenzylguanadine ( (131)I-MIBG). First, in a 15-year-old boy with clinical suspicion of PHEO, the diagnosis was established by biochemical evaluation and confirmed by further imaging studies, including CT and (123)I-MIBG, as PGL in the Zuckerkandl organ. The tumor was completely resected by laparotomy. Second, in a 70-year-old woman presenting with progressive hypertension and palpitations, MR and (123)I-MIBG revealed a singular tumor lesion with abnormal (123)I-MIBG uptake in the Zuckerkandl organ. Due to severe general vascular disease, surgery was not performed and instead the patient underwent (131)I-MIBG therapy. The patient showed a good symptomatic response with improvement of symptoms and no relevant side-effects of therapy.

Reduced cardiac 123I-MIBG uptake reflects cardiac sympathetic dysfunction in de novo Parkinson’s disease

It remains unclear whether cardiac iodine-123-labeled metaiodobenzylguanidine ((123)I-MIBG) uptake is clinically related to autonomic dysfunction on conventional autonomic function testing in de novo Parkinson's disease (PD). We therefore studied the relation between cardiac (123)I-MIBG uptake and cardiovascular autonomic dysfunction in patients with de novo PD. The subjects were 26 patients with de novo PD. The ratio of the average pixel count in the heart to that in the mediastinum was calculated to derive the cardiac (123)I-MIBG uptake. Cardiovascular autonomic function was evaluated on the basis of cardiovascular autonomic response on the Valsalva maneuver (VM), and systolic blood pressure response (SBP) on head-up tilt-table testing (HUT). Patients with de novo PD had significantly reduced cardiac (123)I-MIBG uptake as compared with controls (1.58±0.43 vs. 2.25±0.34, p=0.0001) and cardiovascular autonomic response on the VM. No significant difference in the fall in SBP on HUT was found between patients with de novo PD and the controls. Cardiac (123)I-MIBG uptake in de novo PD was not significantly related to vasomotor sympathetic function, baroreceptor reflex gain, cardiac parasympathetic function, or the changes in SBP on HUT. Cardiac (123)I-MIBG uptake was, however, significantly related to the blood pressure overshoot in phase IV of the VM (r=0.648, p=0.0003). Cardiac (123)I-MIBG uptake began to decrease in association with the reduction in the overshoot of phase IV on the VM. Cardiac (123)I-MIBG uptake clinically reflects cardiac sympathetic dysfunction in de novo PD.

123I-MIBG cardiac uptake and smell identification in parkinsonian patients with LRRK2 mutations

Reduced uptake of 123I- metaiodobenzylguanidine (MIBG) on cardiac gammagraphy and impaired odor identification are markers of neurodegenerative diseases with Lewy bodies (LB) as a pathological hallmark, such as idiopathic Parkinson’s disease (IPD). LRRK2 patients present with a clinical syndrome indistinguishable from IPD, but LB have not been found in some cases. Patients with such mutations could behave differently than patients with IPD with respect to MIBG cardiac uptake and olfaction. We studied 14 LRRK2 patients, 14 IPD patients matched by age, gender, disease duration and severity, and 13 age and gender matched control subjects. Olfaction was analyzed through the University of Pennsylvania Smell Identification Test (UPSIT). MIBG cardiac uptake was evaluated through the H/M ratio. The late H/M was 1.44 ± 0.31 for LRRK2 patients, 1.19 ± 0.15 for PD patients, and 1.67 ± 0.16 for control subjects. LRRK2 patients presented lower but not statistically significant MIBG cardiac uptake than controls (p = 0.08) and significant higher uptake than PD patients (p = 0.04). UPSIT mean scores were 21.5 ± 7.3 for LRRK2 patients, 18.7 ± 6.2 for IPD patients and 29.7 ± 5.7 for control subjects. UPSIT score was lower in both LRRK2 and PD than in controls. In LRRK2 patients a positive correlation was found between myocardial MIBG uptake and UPSIT scores, (R = 0.801, p < 0.001). In LRRK2 patients, MIBG cardiac uptake was less impaired than in PD; a positive correlation between MIBG cardiac uptake and UPSIT scores was observed. As MIBG cardiac reduced uptake and impaired odor identification are markers of LB pathology, this findings may represent neuropathological heterogeneity among LRRK2 patients.

ＩＤＷ法を用いた異なるガンマカメラシステムにおける｀１２３´Ｉ−ＭＩＢＧ Ｈ／Ｍ比のクロスキャリブレーションの検討

(123)I-MIBG Heart-to-Mediastinum activity ratio (H/M) is commonly used as an indicator of relative myocardial (123)I-MIBG uptake. H/M ratios reflect myocardial sympathetic nerve function, therefore it is a useful parameter to assess regional myocardial sympathetic denervation in various cardiac diseases. However, H/M ratio values differ by site, gamma camera system, position and size of region of interest (ROI), and collimator. In addition to these factors, 529 keV scatter component may also affect (123)I-MIBG H/M ratio. In this study, we examined whether the H/M ratio shows correlation between two different gamma camera systems and that sought for H/M ratio calculation formula. Moreover, we assessed the feasibility of (123)I Dual Window (IDW) method, which is a scatter correction method, and compared H/M ratios with and without IDW method. H/M ratio displayed a good correlation between two gamma camera systems. Additionally, we were able to create a new H/M calculation formula. These results indicated that the IDW method is a useful scatter correction method for calculating (123)I-MIBG H/M ratios.

Semi-automated algorithm for calculating heart-to-mediastinum ratio in cardiac Iodine-123 MIBG imaging

BackgroundWe have developed novel software for semi-automatically measuring heart-to-mediastinum (H/M) ratio in cardiac Iodine-123 (123I)-labeled meta-iodobenzylguanidine (MIBG) imaging. Our aim is to improve the reproducibility of the H/M ratio using the semi-automated method as opposed to the manual method. Methods and ResultsThe software algorithm automatically determined the mediastinal region of interest (ROI) using information from 123I-MIBG uptake of the heart, lung, liver, and thyroid after a cardiac circular ROI was manually set. A total of 37 patients who underwent both early and delayed 123I-MIBG imaging was retrospectively selected. The heart-to-mediastinum (H/M) ratios were calculated by both semi-automated and manual methods and assessed for the intra- and inter-observer variability. All H/M ratios were classified into three groups: normal, slight abnormality, and severe abnormality. The H/M ratios with the new method were higher than those obtained manually (P<.001). In the test-retest reliability, the intra-class correlation coefficient from the semi-automated method showed excellent reproducibility for early (0.99) and delayed (0.99) imaging. The Bland-Altman plots demonstrated better agreement using the semi-automated method (a range of 95% limits −0.11 to 0.10) than that in the manual method (−0.34 to 0.27). The inter-observer agreement was also good using the semi-automated method (κ = 0.866). ConclusionsThe H/M ratio using the semi-automated method showed high reproducibility in both early and delayed imaging.

In vitro and in vivo studies of adenovirus-mediated human norepinephrine transporter gene transduction to hepatocellular carcinoma

The clinical value of (131)I-MIBG for targeted imaging and targeted radiotherapy is limited to neural crest-derived tumors expressing human norepinephrine transporters (hNET) protein. To extend (131)I-MIBG-targeted therapy to other nonexpressed hNET tumors, this study investigated the hNET expression in vitro and in vivo in HepG2 hepatoma mediated by recombinant adenovirus encoding the hNET gene (Ad-hNET). For this purpose, the HepG2 cells showed a 4.87-fold increase in (125)I-MIBG uptake after infection with Ad-hNET, and the uptake of (125)I-MIBG could be specifically inhibited by maprotiline. Immunohistological analysis, in vivo biological study and (131)I-MIBG scintigraphic imaging also revealed the high expression of hNET protein in hepatoma. This in vitro and in vivo studies demonstrate the feasibility of hNET gene transfer, meditated by adenovirus vector, could extend to tumors other than those derived from the neural crest, which provides a sound foundation for further investigation of hepatocellular carcinoma-targeted radiotherapy mediated by adenovirus transfection with hNET gene.

Iodine‐123 metaiodobenzylguanidine scintigraphic assessment of pulmonary vascular status in patients with chronic obstructive pulmonary disease

Lung uptake of iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) is used as an indicator of pulmonary endothelial function. Decreased lung uptake of ¹²³I-MIBG has been demonstrated in patients with COPD as compared with normal subjects. The present study was performed to examine the relationship between lung uptake of ¹²³I-MIBG and pulmonary artery pressure (Ppa) at rest and during exercise, in patients with COPD. ¹²³I-MIBG scintigraphy was performed in 19 patients with COPD. Anterior planar images were acquired 15 min after the injection of ¹²³I-MIBG, and the total lung to upper mediastinum ratio (LMR) was calculated for both lungs. Right heart catheters were used to monitor Ppa continuously at rest and during exercise. Exercise was performed on an electrically braked bicycle ergometer at a constant workload of 25 W for 3 min. In COPD patients the LMR were not correlated with the pulmonary function parameters measured before exercise, including FEV₁, PaO₂, DL(CO), or Ppa at rest. However, the percentage increase in Ppa during exercise was significantly correlated with LMR. Evaluation of the kinetics of lung uptake of ¹²³I-MIBG may be a novel scintigraphic tool for the assessment of exercise-induced pulmonary hypertension in patients with COPD.

Cardiac (123)I-metaiodobenzylguanidine Scintigraphy in a Patient with Familial Parkinsonism with Parkin Gene Mutation.

A decreased cardiac 123I-metaiodobenzylguanidine (123I-MIBG) uptake has been used as a powerful tool to identify Lewy body disease, such as idiopathic parkinson’s disease (IPD). We performed cardiac 123I-MIBG scintigraphy in patient with autosomal recessive juvenile parkinsonism (ARJP) with parkin gene mutation (PARK2). The findings showed normal cardiac 123I-MIBG uptake. Therefore, although the clinical features of ARJP are sometimes quite similar to those of late-onset IPD, cardiac 123I-MIBG scintigraphy may be used as a valuable tool to identify patients with IPD and to distinguish them from patients with other parkinsonian syndromes.

Intérêt de la tomoscintigraphie cardiaque à la 123I-mIBG couplée à la perfusion myocardique dans le diagnostic de l’atrophie multisystématisée

Objective The aim of this prospective study is to assess the pertinence of using 123I-mIBG myocardial tomoscintigraphy coupled with perfusion scintigraphy as a diagnostic tool, to discriminate between multiple system atrophy (MSA) and idiopathic Parkinson's disease (PD) at first guided by clinical data and L-DOPA tests. Material and methods Forty patients, aged from 43 to 78 years (median 62 years) with Parkinson's syndrome were studied. Nineteen had a diagnosis of PD (criteria of brain bank) and 21 AMS (Gibbs criteria). All were given test to acute L-DOPA. Chest-centered planar imaging (128 × 128 matrix, 5 minutes of duration) is performed at 1 hour and 4 hours after injection of 220 MBq of 123I-mIBG, in addition a non-synchronised tomoscintigraphy (64 × 64 matrix, 32 images of 50 seconds , zoom 1.45) was performed after the 4th hour and 15 minutes after injection of 200 to 400 MBq of 99mTc-tetrofosmin. Besides neurological data, the parameters retained for comparison purposes with 123I-mIBG cardiac tomoscintigraphy were patients’ age, duration of disease and L-DOPA test results. Two regions of interest (ROI) identical in size and in shape are used for 123I-mIBG uptake quantifications (H/M and washout [Wo]). The first one was placed in projection of mediastinum (M) and the other one in projection of heart (H). Results We found an overall decreased uptake of the myocardial 123I-mIBG without perfusion abnormality in 15 of 19 patients with PD and 11 among them were L-DOPA sensitive (L-DOPA test greater than 30%). Normal tracer uptake with 123I-mIBG associated with an almost quite normal perfusion was seen in 15 of 21 patients with MSA and they were little or not L-DOPA sensitive (L-DOPA test less than 30%). Therefore, 10 discordant cases (25%) between cardiac scintigraphy and clinical evolution of disease with also discordant L-DOPA tests were observed. In the PD group, quantification of data enhanced the diagnostic decision with low heart to mediastinum ratio (H/M) (1.32 ± 0.15 at the early stage and 1.25 ± 0.13 at the later stage). In the MSA group, the uptake of 123I-mIBG (1.66 ± 0.43 at the early stage and 1.72 ± 0.42 at the later stage) was comparable to literature data, however, with significant inter-individual variations. The association of data of scintigraphy with L-DOPA test allows to improve sensitivity in 84% and specificity in 90.5%. Conclusion Our prospective study of 40 cases shows the relevance of cardiac sympathetic postganglionic imaging with 123I-mIBG coupled with myocardial perfusion scintigraphy to discriminate between MSA and PD with a higher sensitivity (71.4%) compared to the test with L-DOPA but a lower specificity (78.9%) than the L-DOPA. The difficulty of diagnosis is firstly linked to damage occurring to both the pre- and postganglionic sympathetic systems in patients with MSA and secondly to the integrity of the sympathetic nerve endings in patients with PD. However, the association of data of scintigraphy with L-DOPA test show a significant improvement of sensibility (84%).

Olfactory dysfunction and cardiovascular dysautonomia in Parkinson’s disease

Several studies have reported that olfactory dysfunction is an early neuropathological manifestation of Parkinson's disease (PD). Reduced cardiac meta-iodobenzylguanidine ((123)I-MIBG) uptake may be one of the earliest signs of PD. We studied the relation of olfactory dysfunction to cardiovascular dysautonomia in patients with PD. The study group comprised 66 patients with PD (70.5 years) and 26 controls (70.3 years) for olfactory assessment, 21 controls (72.1 years) for cardiac (123)I-MIBG scintigraphy and heart rate variability (HRV), assessed using the coefficient of variation for RR intervals (HRV), and 23 controls (69.2 years) for orthostatic blood pressure response. Olfactory function was assessed by the odor stick identification test Japan (OSIT-J), and cardiovascular autonomic function was evaluated by (123)I-MIBG scintigraphy of the heart, the fall in orthostatic blood pressure, and HRV. Patients with PD had a significantly lower OSIT-J score than did the controls (4.1 +/- 3.0 vs. 9.9 +/- 1.7, p = 0.001). The OSIT-J score was unrelated to variables other than gender, including age, disease duration, motor score on the unified Parkinson's disease rating scale, score on the mini-mental state examination, motor phenotype, visual hallucinations, and dopaminergic medication on multiple regression and logistic regression analyses. The OSIT-J score was related to the heart/mediastinum ratio of cardiac (123)I-MIBG uptake, the fall in orthostatic blood pressure, and HRV, after adjustment for other clinical variables. Olfactory dysfunction in PD was, thus, significantly related to both cardiac sympathetic and parasympathetic dysfunction, as well as vascular sympathetic dysfunction. As non-motor symptoms of PD, olfactory dysfunction and autonomic network failure appear to be closely related in PD.

Cardiac 123I-MIBG uptake is reduced more markedly in patients with REM sleep behavior disorder than in those with early stage Parkinson's disease

We investigated cardiac uptake of 123I-metaiodobenzylguanidine (MIBG) in patients with REM sleep behavior disorder (RBD) and compared the findings with those of idiopathic Parkinson's disease (IPD). Thirteen RBD, 222 IPD and 50 controls underwent cardiac 123I-MIBG scintigraphy. Resulting heart-to-mediastinum (H/M) ratios were significantly lower in patients with RBD and IPD as compared to the control ratios. H/M ratios were lower for delayed than for early images in patients with RBD and IPD; whereas, the controls had higher ratios for delayed images. H/M ratios were significantly lower for patients with RBD than for those with IPD at Hoehn and Yahr stages 1 and 2. Disease duration did not differ between the two groups. Our study revealed that cardiac 123I-MIBG uptake was more markedly reduced in patients with RBD than in those with early stage IPD. RBD may not necessarily be a prodromal condition of IPD with respect to cardiac 123I-MIBG uptake results.

Fluvastatin Attenuates Diabetes-Induced Cardiac Sympathetic Neuropathy in Association With a Decrease in Oxidative Stress

Increased oxidative stress might contribute to diabetic (DM) neuropathy, so the effects of long-term treatment with fluvastatin (FL) on myocardial oxidative stress and cardiac sympathetic neural function were investigated in diabetic rats. FL (10 mg . kg(-1) . day(-1), DM-FL) or vehicle (DM-VE) was orally administered for 2 weeks to streptozotocin-induced DM rats. Cardiac oxidative stress was determined by myocardial 8-iso-prostaglandin F(2alpha) (PGF(2alpha)) and NADPH oxidase subunit p22(phox) mRNA expression. Sympathetic neural function was quantified by autoradiography using (131)I- and (125)I-metaiodobenzylguanidine (MIBG). FL did not affect plasma glucose levels but remarkably decreased PGF(2alpha) levels compared with DM-VE rats (13.8+/-9.2 vs 175.0+/-93.9 ng/g tissue), although PGF(2alpha) levels were below the detection limit in non-DM rats. FL significantly reduced myocardial p22(phox) mRNA expression. Cardiac (131)I-MIBG uptake was lower in DM-VE rats than in non-DM rats, but the decrease was attenuated in DM-FL rats (1.31+/-0.08, 1.88+/-0.22, and 1.58+/-0.18 %kg dose/g, respectively, P<0.01). Cardiac MIBG clearance was not affected by the induction of DM or by FL, indicating that the reduced MIBG uptake in DM rats might result from impaired neural function. FL ameliorates cardiac sympathetic neural dysfunction in DM rats in association with attenuation of increased myocardial oxidative stress.

Multipoint analysis of reduced 125I-meta-iodobenzylguanidine uptake and norepinephrine turnover in the hearts of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine-induced parkinsonism

(125)I-Meta-iodobenzylguanidine (MIBG) cardiac uptake is reduced in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP)-induced parkinsonism, although the cause of disturbance of norepinephrine (NE) turnover is unclear. C57BL6 mice (15 weeks old) were divided into six groups (n=14 each) according to the timing of MPTP injection (40 mg/kg) before (125)I-MIBG: Group A, control (no MPTP injection); Group B, 1 day; Group C, 4 days; Group D, 7 days; Group E, 21 days; Group F, 7, 14 and 21 days. (125)I-MIBG (0.185 MBq) was injected and the cardiac percentage injected dose per gram of tissue (%ID/g), dopamine (DA) and NE concentrations were measured. The cardiac maximal binding potential (B(max)) of NE transporter (NET) was also calculated in 20 mice per group. The %ID/g of B, C, D, E and F mice were significantly lower than in A; those of C, D and E were significantly higher than in B; and that of F was significantly lower than in E. The DA concentrations were similar among all groups. The NE concentrations of B, C and F mice were significantly lower than in A, while those of C, D, E and F were significantly higher than in B, and that of F was significantly lower than in E. The B(max) of NET in B was significantly lower than in A. Thus, MPTP causes rapid reductions in cardiac (125)I-MIBG uptake and B(max) of NET, followed by partial recovery of (125)I-MIBG uptake. Changes in cardiac (125)I-MIBG uptake and NE turnover were closely related in postganglionic cardiac sympathetic nerve terminals in mice with MPTP-induced parkinsonism.

Validation of cardiac 123I-MIBG scintigraphy in patients with Parkinson’s disease who were diagnosed with dopamine PET

The aim of this study was to evaluate the diagnostic potential of cardiac (123)I-labelled metaiodobenzylguanidine ((123)I-MIBG) scintigraphy in idiopathic Parkinson's disease (PD). The diagnosis was confirmed by positron emission tomography (PET) imaging with (11)C-labelled 2beta-carbomethoxy-3beta-(4-fluorophenyl)-tropane ((11)C-CFT) and (11)C-raclopride (together designated as dopamine PET). Cardiac (123)I-MIBG scintigraphy and dopamine PET were performed for 39 parkinsonian patients. To estimate the cardiac (123)I-MIBG uptake, heart to mediastinum (H/M) ratios in early and delayed images were calculated. On the basis of established clinical criteria and our dopamine PET findings, 24 patients were classified into the PD group and 15 into the non-PD (NPD) group. Both early and delayed images showed that the H/M ratios were significantly lower in the PD group than in the NPD group. When the optimal cut-off levels of the H/M ratio were set at 1.95 and 1.60 in the early and delayed images, respectively, by receiver-operating characteristic analysis, the sensitivity of cardiac (123)I-MIBG scintigraphy for the diagnosis of PD was 79.2 and 70.8% and the specificity was 93.3 and 93.3% in the early and delayed images, respectively. In the Hoehn and Yahr 1 and 2 PD patients, the sensitivity decreased by 69.2 and 53.8% in the early and delayed images, respectively. In early PD cases, cardiac (123)I-MIBG scintigraphy is of limited value in the diagnosis, because of its relatively lower sensitivity. However, because of its high specificity for the overall cases, cardiac (123)I-MIBG scintigraphy may assist in the diagnosis of PD in a complementary role with the dopaminergic neuroimaging.

Transient left ventricular dysfunction syndrome: Patho-physiological bases through nuclear medicine imaging

Takotsubo cardiomyopathy (TTC) is a novel heart disease, mimicking acute myocardial infarction. The term "transient left ventricular dysfunction syndrome" (TLVDS) seems to be more appropriate since variant forms of TTC sparing apical segments (mid-ventricular ballooning syndrome (MVBS) and inverted TTC) have been described. Patho-physiological bases of TLVDS remain poorly understood and its optimal management is until now empirical. Our aim was to characterize patho-physiological mechanisms of TLVDS by means of nuclear medicine procedures and to discuss the clinical usefulness of isotopic imaging for a non-invasive diagnosis of TLVDS. During the sub acute phase, eighteen patients with TLVDS (13 TTC and 5 MVBS) underwent myocardial (99m)Tc-tetrofosmin or (201)Thallium Gated Single Photon Emission Computed Tomography (G-SPECT) (n=11), (123)I-mIBG SPECT (n=8) and (18)F-FDG Gated Positron Emission Tomography (G-PET) (n=15), assessing respectively LV perfusion, sympathetic innervation and glucose metabolism. Hypocontractile LV segments were characterized by normal perfusion but reduced uptake of (18)F-FDG and (123)I-mIBG. Topography and extent of metabolic defects and innervation abnormalities were largely overlapping. Follow-up (123)I-mIBG SPECT and (18)F-FDG G-PET were performed in selected patients showing rapid normalization of LV motion and progressive improvement of both glucose metabolism and sympathetic innervation. With the hypothesis of neurogenic stunned myocardium as the central causative mechanism of TLVDS, (123)I-mIBG SPECT seems to be the most specific diagnostic technique. Sympathetic function and glucose metabolism seem to be strictly correlated in the hypocontractile LV segments. Finally, our results underline the role of nuclear imaging in the setting of patho-physiological mechanisms of TLVDS.