123I metaiodobenzylguanidine (MIBG) uptake predicts early relapse of neuroblastoma using semi-quantitative SPECT/CT analysis

Annals of Nuclear Medicine - 123I metaiodobenzylguanidine (MIBG) scintigraphy is a useful tool for the diagnosis of neuroblastoma (NB). MIBG uptake is correlated with norepinephrine transporter...     

Quantitation of cardiac sympathetic innervation in rabbits using 11C-hydroxyephedrine PET: relation to 123I-MIBG uptake

Purpose Although ¹¹C-hydroxyephedrine (¹¹C-HED) PET is used to map cardiac sympathetic innervation, no studies have shown the feasibility of quantitation of ¹¹C-HED PET in small- to medium-sized animals. Furthermore, its relation to ¹²³I-MIBG uptake, the most widely used sympathetic nervous tracer, is unknown. The aims of this study were to establish in vivo sympathetic nerve imaging in rabbits using ¹¹C-HED PET, and to compare the retention of ¹¹C-HED with that of ¹²³I-MIBG.Methods Twelve rabbits were assigned to three groups; control (n=4), chemical denervation by 6-hydroxydopamine (6-OHDA) (n=4) and reserpine treated to inhibit vesicular uptake (n=4). After simultaneous injection of ¹¹C-HED and ¹²³I-MIBG, all animals underwent dynamic ¹¹C-HED PET for 40 min with arterial blood sampling. The ¹¹C-HED retention fraction and normalised ¹¹C-HED activity measured by tissue sampling were compared with those measured by PET.Results Both the ¹¹C-HED retention fraction and the normalised ¹¹C-HED activity measured by PET correlated closely with those measured by tissue sampling (R=0.96027, p<0.001 and R=0.97282, p<0.001, respectively). Inhibition study by 6-OHDA resulted in a significant reduction in retention (90%) for both ¹¹C-HED and ¹²³I-MIBG. Reserpine pretreatment reduced ¹¹C-HED retention by 50%, but did not reduce ¹²³I-MIBG retention at 40 min after injection.Conclusion Non-invasive quantitation of cardiac sympathetic innervation using ¹¹C-HED PET is feasible and gives reliable estimates of cardiac sympathetic innervation in rabbits. Additionally, although both ¹¹C-HED and ¹²³I-MIBG are specific for sympathetic neurons, ¹¹C-HED may be more specific for intravesicular uptake than ¹²³I-MIBG in some situations, such as that seen in reserpine pretreatment.     

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

123I-Metaiodobenzylguanidine (MIBG) is expected to be useful agent for functional evaluation of the myocardial sympathetic innervation. The aim of this paper is to investigate serial change of 123I-MIBG myocardial concentration in patients (pts) with dilated cardiomyopathy (DCM) as compared with 201Tl uptake. Eight pts with DCM and six non-cardiac subjects (controls) were examined. After injection of 111 MBq (3mCi) 201Tl and 111 MBq (3 mCi) 123I-MIBG, simultaneous myocardial imaging in anterior view was performed for both tracers in every 30-60 minutes during 5 hours (6 images). Myocardial uptake ratio per pixel to the injected dose was calculated for each tracer with background and cross-talk correction on each image. In pts with DCM, myocardial uptake ratio of 123I-MIBG did not differ significantly from that of controls. The washout of 123I-MIBG from the myocardium, however, was significantly increased in pts with DCM as compared with controls. The % decrease of the radioactivity in 3 hours was 46.9 +/- 13.8% in DCM, whereas 18.0 +/- 7.7% in controls (p less than 0.05). Especially, the decrease in the early phase (less than 1 hour) was significantly larger in DCM than controls (21.2 +/- 7.5% vs 5.3 +/- 4.0%, p less than 0.01). For 201Tl, on the other hand, neither uptake ratio nor washout rate, differed significantly between the two. In conclusion, the rapid washout of 123I-MIBG in the early phase may reflect some sympathetic dysfunction in pts with DCM.     

Assessment of most appropriate background subtraction method for quantification of 123I-metaiodobenzylguanidine (MIBG) myocardial uptake by comparing with plasma ANP and BNP

BACKGROUND: Quantification of 123I-metaiodobenzylguanidine (MIBG) myocardial uptake is widely accepted as a useful tool for estimating the severity of congestive heart failure. However, most reliable method has not been determined yet because of the difficulty of background (BG) subtraction. In this study, the most appropriate BG subtraction method was evaluated as compared with plasma atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine (NEP) and left ventricular ejection fraction (LVEF). METHODS: Twenty-one patients with chronic heart failure were examined. After bolus injection of 123I-MIBG (111 MBq), dynamic anterior chest images were collected every second for 2 minutes. Planar anterior chest images were obtained 15 minutes (early image) and 4 hours later (delayed image) respectively. The parameters for quantification of 123I-MIBG myocardial uptake used in this study were heart to mediastinum ratio (H/M), myocardial washout rate and uptake ratio. Background was calculated using the region of interest (ROI) placed over a part of upper mediastinum, whole upper mediastinum, right lung and pericardial space respectively. The values of these parameters were calculated with and without BG subtraction and compared with plasma ANP, BNP and others. RESULTS: H/M did not correlate with ANP or BNP. Myocardial washout rate without BG subtraction showed significant correlation with ANP (p < 0.01) and BNP (p < 0.05). After BG subtraction employing ROI placed over the part of upper mediastinum and whole upper mediastinum, myocardial washout rate showed better correlation with BNP (p < 0.01). Myocardial uptake ratio did not showed any correlation with ANP or BNP without BG subtraction. However, myocardial uptake ratio showed significant correlation with BNP (p < 0.05) after subtraction of upper mediastinal BG. BG subtraction using ROI over right lung or pericardial area revealed poor results in both myocardial washout rate- and uptake ratio. CONCLUSION: BG subtraction using ROI over the upper mediastinum is likely to be suitable for quantitative analysis of 123I-MIBG myocardial scintigram.     

Assessment of global cardiac I-123 MIBG uptake and washout using volumetric quantification of SPECT acquisitions

Background

Assessment of cardiac innervation using single-photon emission computer tomography (SPECT) is less established than planar imaging, but may be more suitable for quantification. Therefore, a volumetric quantification of I-123 MIBG SPECT acquisitions was performed. Reproducibility, the effects of extra cardiac I-123 MIBG uptake and the relation with conventional planar indices were evaluated.

Methods

54 patients referred for planar and SPECT I-123 MIBG acquisitions were included. Ellipsoidal or box-shaped volumes of interest were placed on the left ventricle, cardiac lumen, mediastinum, lung and liver. SPECT segmentation was performed twice in all patients. Indices were determined based on the heart-to-mediastinum (HM), myocardial wall-to-mediastinum and myocardial wall-to-lumen regions. HM ratios and washout rates were also determined based on anterior planar images.

Results

Cardiac count densities were highly reproducible (CV 1.5-5.4, ICC 0.96-0.99) and inter-rater variability was low (CV 1.8-6.8, ICC 0.94-0.99). Mediastinal uptake was an important explanatory variable of uptake in the entire heart (early R ²?=?0.36; delayed R ² =0.43) and myocardial wall (early R ²?=?0.28; delayed R ²?=?0.37). Lung washout was an explanatory variable of organ washout of the heart (heart R ²?=?0.38; myocardial wall R ²?=?0.33). In general, SPECT indices showed moderate-to-good correlations with the planar uptake (PCC 0.497-0.851).

Conclusion

By applying a volumetric segmentation method we were able to segment the heart in all patients. SPECT I-123 MIBG quantification was found to be highly reproducible and had a moderate to good correlation with the planar indices.     

Estimation of I-123 metaiodobenzylguanidine (MIBG) myocardial washout

A crosstalk from I-123 to Tl-201 (Tl) window was 35 +/- 30% (mean +/- SD) and 30 +/- 10% in a myocardial phantom and the images of 6 patients respectively. However, the crosstalk from Tl to I-123 was approximately 1% in each. I-123 MIBG (MIBG) and Tl myocardial SPECT images were recorded in 3 normal volunteers (N), 10 patients with myocardial infarction (MI), and 4 with dilated cardiomyopathy (DCM). The MIBG and Tl imagings were performed on the other day to avoid the crosstalk. Myocardial washout rates (WR) of Tl and MIBG were derived from 15 min and 4 hour images. WR of Tl was approximately 36% in each group. On the other hand, WR of MIBG in DCM (52 +/- 7%) and MI (41 +/- 14%) groups were statistically higher than in N (24 +/- 7%) group. Thus WR of MIBG would be useful to detect abnormalities in adrenergic nervous system.     

High uptake of 123I-metaiodobenzylguanidine related to olfactory neuroblastoma revealed by single-photon emission CT

We studied a case of olfactory neuroblastoma by noting 123I-metaiodobenzylguanidine (MIBG) uptake revealed by single-photon emission CT (SPECT). MR imaging revealed an enhancing tumor extending from the left nasal cavity to the bilateral anterior frontal cranial fossae. SPECT revealed high 123I-MIBG uptake in the enhancing tumor. SPECT-revealed 123I-MIBG uptake appears to be clinically useful for distinguishing olfactory neuroblastomas from other tumors, especially suprasellar meningiomas.     

Estimation of regional myocardial sympathetic neuronal function with I-123 metaiodobenzylguanidine (MIBG) myocardial images in patients with cardiomyopathy

I-123 Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic neuronal endings. Sympathetic neuronal function in 10 patients with cardiomyopathy under stable state were studied by using MIBG and Tl-201 (Tl) SPECT images with 50% cut off level. For myocardial imaging MIBG and Tl were simultaneously injected and collected (dual injection and dual collection mode; Dd mode). Four hours delayed images were also collected. Three types of abnormal findings were noted in MIBG images in combination with Tl images. 1) Enhancement of regional MIBG washout with otherwise normal MIBG and Tl uptake in infero-lateral wall were noted in 5 patients with history of congestive heart failure (Pathophysiologically acceleration of regional sympathetic neuronal function was suspected. Mean washout ratio is 63 +/- 7% vs. 45 +/- 10% in normal region). 2) In 3 patients with dilated cardiomyopathy increase of MIBG/Tl (M/T) ratio was noted in basal septal wall (Sympathetic neuronal function is abnormally accelerated in the region with depressed coronary perfusion. Exaltation of regional sympathetic neuronal function was suspected. Mean M/T ratio is 1.6. Tentative normal range is from 0.8 to 1.20). 3) In 2 patients with dilated cardiomyopathy under severe congestive heart failure defects of MIBG uptake with normal Tl uptake were noted (Sympathetic neuronal function was depleted in spite of normal coronary perfusion. Depletion of myocardial catecolamine was suspected. M/T ratio is 0.75 and 0.7 respectively). Heterogeneous abnormality of sympathetic neuronal function was noted in MIBG images. This findings corresponded to report about heterogeneous myocardial catecholamine concentrations in hearts of recipients of transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Whole-body PET/CT with 11C-meta-hydroxyephedrine in tumors of the sympathetic nervous system: feasibility study and comparison with 123I-MIBG SPECT/CT.

The 11C-labeled tracer meta-hydroxyephedrine (11C-HED) is a noradrenaline analog that was developed to visualize the sympathetic nervous system with PET. Initial clinical studies show a rapid uptake of 11C-HED in localized tumors of this system. Whole-body imaging with 11C-HED PET is now possible as PET/CT scanners allow a rather short examination time. The aim of this study was to evaluate the feasibility of whole-body 11C-HED PET/CT for examination of tumors of the sympathetic nervous system and to directly compare the results with 123I-labeled meta-iodobenzylguanidine (123I-MIBG) scintigraphy, including SPECT/CT. METHODS: In 19 consecutive patients, 9 mo to 68 y old (median, 32 y), 24 whole-body 11C-HED PET/CT (low-dose CT) examinations were performed. Scans were compared with attenuation-corrected 123I-MIBG SPECT/CT scans (24-h scan, low-dose CT). The intensity of tracer accumulation above background was visually analyzed in both scans, PET and SPECT, using a 4-value scale. In 11C-HED PET, mean and maximum standardized uptake values were determined for all lesions. RESULTS: In 14 patients with 19 pairs of examinations, the following tumors were confirmed histologically: 6 neuroblastomas, 5 pheochromocytomas, 1 ganglioneuroblastoma, and 2 paragangliomas. In 5 patients, each having 1 pair of examinations, clinical follow-up and/or histologic examination did not reveal any tumor deriving from the sympathetic nervous system. 11C-HED PET/CT detected 80 of 81 totally depicted tumor lesions (sensitivity, 0.99; soft tissue, 61; bone, 19). 123I-MIBG SPECT/CT detected 75 of 81 lesions (sensitivity, 0.93; soft tissue, 56; bone, 19). With both methods, there were no false-positive lesions. The tumor-to-background contrast of 11C-HED uptake was higher in comparison with 123I-MIBG uptake in 26 lesions (0.32; soft tissue, 18; bone, 8), equal in 39 lesions (0.48; soft tissue, 30; bone, 9), and lower than 123I-MIBG uptake in 16 lesions (0.20; soft tissue, 14; bone, 2). CONCLUSION: Whole-body imaging using 11C-HED PET/CT is feasible in the clinical setting of patients with tumors of the sympathetic nervous system. 11C-HED PET/CT detected more tumor lesions than 123I-MIBG SPECT/CT. However, tumor-to-background contrast of 11C-HED in lesions can be higher, equal, or lower compared with 123I-MIBG.     

Brown fat imaging with (18)F-6-fluorodopamine PET/CT, (18)F-FDG PET/CT, and (123)I-MIBG SPECT: a study of patients being evaluated for pheochromocytoma.

Several radiopharmaceuticals such as (18)F-FDG, (123)I-metaiodobenzylguanidine (MIBG), and (99m)Tc-tetrofosmin have demonstrated uptake in brown adipose tissue (BAT). It is important to recognize these normal variants so that they are not misinterpreted as a significant pathologic state. In addition, these radiopharmaceuticals may shed light on BAT physiology. (18)F-6-fluorodopamine (F-DA) is being used as a PET radiopharmaceutical to image adrenergic innervation and suspected pheochromocytoma. Past reports have suggested that BAT is increased in pheochromocytoma patients. METHODS: The images of 96 patients evaluated with (18)F-F-DA or (18)F-FDG PET/CT for known or suspected pheochromocytoma were reviewed retrospectively to determine whether localized uptake of a pattern typically associated with BAT was present. When available, contemporaneous images obtained using (123)I-MIBG were also reviewed for the presence of BAT. RESULTS: Of 67 patients imaged with (18)F-F-DA, BAT was found in 17.9%. Of 83 patients imaged with (18)F-FDG, 19.2% had BAT. Discordant findings related to uptake in BAT were often seen in patients studied with (18)F-FDG, (18)F-F-DA, or (123)I-MIBG. Overall, 26 (27.0%) of 96 patients showed BAT on at least 1 of the 3 imaging modalities. CONCLUSION: (18)F-F-DA can image BAT, most likely by localizing to sympathetic innervations in a manner similar to (123)I-MIBG. Patients with pheochromocytoma may have a greater BAT tissue mass or activation because of elevated levels of circulating catecholamines. Quantitative PET with (18)F-FDG and (18)F-F-DA may have a role in in vivo studies of BAT physiology in humans or animal models.     

Kombinierte Hybridsysteme (PET/CT, SPECT/CT) versus multimodale Bildgebung mit getrennten Systemen

With increasing use of combined PET/CT scanners in the last few years, multimodality imaging (Nuclear Medicine/Radiology) found its way into clinical routine diagnostics. In this overview, necessary components for multimodality imaging, strategies for image analysis and image presentation, and diagnostic goals of combined imaging are demonstrated and discussed. A special focus is on the question, whether combined scanners can be replaced by a software approach with separated modalities. Advantages and limitations of multimodality imaging with combined or separated scanners are shown.     

Reproducibility of planar 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy in patients with heart failure

Purpose

Despite its high prognostic value, widespread clinical implementation of ¹²³I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is hampered by a lack of validation and standardization. The purpose of this study was to assess the reliability of planar ¹²³I-MIBG myocardial scintigraphy in patients with heart failure (HF).

Methods

Planar myocardial MIBG images of 70 HF patients were analysed by two experienced and one inexperienced observer. The reproducibility of early and delayed heart-to-mediastinum (H/M) ratios, as well as washout rate (WR) calculated by two different methods, was assessed using the intraclass correlation coefficient (ICC) and the Bland-Altman analysis. In addition, a subanalysis in patients with a very low H/M ratio (delayed H/M ratio <1.4) was performed. The delayed H/M ratio was also assessed using fixed-size oval and circular cardiac regions of interest (ROI).

Results

Intra- and interobserver analyses and experienced versus inexperienced observer analysis showed excellent agreement for the measured early and delayed H/M ratios and WR on planar ¹²³I-MIBG images (the ICCs for the delayed H/M ratios were 0.98, 0.96 and 0.90, respectively). In addition, the WR without background correction resulted in higher reliability than the WR with background correction (the interobserver Bland-Altman 95?% limits of agreement were ?2.50 to 2.16 and ?10.10 to 10.14, respectively). Furthermore, the delayed H/M ratio measurements remained reliable in a subgroup of patients with a very low delayed H/M ratio (ICC 0.93 for the inter-observer analysis). Moreover, a fixed-size cardiac ROI could be used for the assessment of delayed H/M ratios, with good reliability of the measurement.

Conclusion

The present study showed a high reliability of planar ¹²³I-MIBG myocardial scintigraphy in HF patients, confirming that MIBG myocardial scintigraphy can be implemented easily for clinical risk stratification in HF.     

Clinical performance and radiation dosimetry of no-carrier-added vs carrier-added 123I-metaiodobenzylguanidine (MIBG) for the assessment of cardiac sympathetic nerve activity

Purpose We hypothesized that assessment of myocardial sympathetic activity with no-carrier-added (nca) ¹²³I-meta-iodobenzylguanidine (MIBG) compared to carrier-added (ca) ¹²³I-MIBG would lead to an improvement of clinical performance without major differences in radiation dosimetry. Methods In nine healthy volunteers, 15 min and 4 h planar thoracic scintigrams and conjugate whole-body scans were performed up to 48 h following intravenous injection of 185 MBq ¹²³I-MIBG. The subjects were given both nca and ca ¹²³I-MIBG. Early heart/mediastinal ratios (H/M), late H/M ratios and myocardial washout were calculated. The fraction of administered activity in ten source organs was quantified from the attenuation-corrected geometric mean counts in conjugate views. Radiation-absorbed doses were estimated with OLINDA/EXM software. Results Both early and late H/M were higher for nca ¹²³I-MIBG (ca ¹²³I-MIBG early H/M 2.46 ± 0.15 vs nca ¹²³I-MIBG 2.84 ± 0.15, p = 0.001 and ca ¹²³I-MIBG late H/M 2.69 ± 0.14 vs nca ¹²³I-MIBG 3.34 ± 0.18, p = 0.002). Myocardial washout showed a longer retention time for nca ¹²³I-MIBG (p < 0.001). The effective dose equivalent (adult male model) for nca ¹²³I-MIBG was similar to that for ca ¹²³I-MIBG (0.025 ± 0.002 mSv/MBq vs 0.026 ± 0.002 mSv/MBq, p = 0.055, respectively). Conclusion No-carrier-added ¹²³I-MIBG yields a higher relative myocardial uptake and is associated with a higher myocardial retention. This difference between nca ¹²³I-MIBG and ca ¹²³I-MIBG in myocardial uptake did not result in major differences in estimated absorbed doses. Therefore, nca ¹²³I-MIBG is to be preferred over ca ¹²³I-MIBG for the assessment of cardiac sympathetic activity.     

Study of sympathetic nervous function under effort induced ischemia in patients with angina pectoris with I-123 metaiodobenzylguanidine (MIBG) myocardial SPECT images

I-123 metaiodobenzylguanidine (MIBG) is a norepinephrine analog, which can be used to study the sympathetic nervous function of the heart. With MIBG myocardial SPECT images sympathetic nervous function under effort induced ischemia were studied in 18 patients with significant coronary artery lesions. In 5 patients with effort induced ischemic region in stress T1-201 myocardial images rest MIBG images were collected and then exercise stress test was performed. Patients continued exercising for 3 minutes after onset of symptom. Post-stress MIBG images were collected. Definite ischemic region was noted in stress Tl-201 myocardial images, however no differences were noted between rest and post-stress MIBG images. These results suggested that exercise induced ischemia did not enhance release of uptaken MIBG. In 13 patients with significant coronary artery lesions symptom-limited exercise stress test was performed MIBG and Tl-201 were simultaneously injected at onset of symptom and patients continued exercising for an additional one minute. In 6 cases (46%, 6/13) MIBG defects with Tl-201 uptake were noted. These results showed that exercise induced ischemia depressed net MIBG uptake and that sympathetic nervous function (MIBG images) may be more sensitive to ischemic damage than muscle (Tl-201 images). It is suggested that exercise induced ischemia depressed reuptake of norepinephrine at sympathetic nervous endings. MIBG myocardial SPECT images may be useful for evaluating sympathetic nervous function under ischemia.