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.     

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)     

Myocardial fatty acid imaging with 123I-labelled 9-methyl-branched pentadecanoic acid (9MPA) using SPET

123I-labelled 15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid (9MPA) is a modified long-chain fatty acid that shows some beta-oxidation. Some basic aspects of this fatty acid, including myocardial uptake, distribution, clearance and differences from 201Tl myocardial perfusion, have yet to be evaluated. An average of 150 MBq of 123I-9MPA was injected intravenously into 16 patients with coronary artery disease. Planar images were obtained 45, 120 and 240 min post-injection, and single photon emission tomography (SPET) was performed at the initial (5 min), middle (45 min) and late (120 min) phases after injection. Myocardial uptake and clearance were evaluated by planar imaging, and a segmental comparison between 123I-9MPA and reinjection or resting 201Tl was performed on the SPET images. 123I-9MPA showed good uptake between 5 and 60 min, but a severe decrease was seen after 120 min in three (19%) patients. The heart-to-mediastinum ratio was 1.68 +/- 0.19, 1.55 +/- 0.19 and 1.40 +/- 1.40 at 45, 120 and 240 min, respectively. The washout rate after background subtraction was 28% for 45 min to 2 h and 47% for 45 min to 4 h. The segmental comparison (n = 182) between 123I-9MPA and 201Tl showed complete agreement of 72, 75 and 65% at 10, 45 and 120 min, respectively. The grading of the uptake of 123I-9MPA was less than that of 201Tl in 20-30% of the segments indicating myocardial fatty acid metabolic impairment relative to perfusion. The regional clearance from 5 to 120 min in the reduced-count region was lower than that in the normal region (28 +/- 7% vs 36 +/- 8%, P < 0.01). All 123I-9MPA SPET images showed good contrast if the data were acquired within 60 min. Based on the clearance of 123I-9MPA from the myocardium, imaging within 120 min is desirable. A mismatch of fatty acids and perfusion was seen in one-quarter of patients, and differential regional clearance may be clinically significant and should be investigated.     

A new method for crosstalk correction in simultaneous dual-isotope myocardial imaging with Tl-201 and I-123

We have developed a new method of crosstalk correction in simultaneous dual-isotope imaging with Tl-201 and I-123 by using crosstalk ratios and a blurring filter. Single isotope myocardial studies (10 for Tl-201 and 7 for I-123) were performed with a dual energy window acquisition mode and two low energy general-purpose collimators. Then two planar images acquired with dual energy windows for a Tl-201 line source and an I-123 line source were obtained to measure line spread functions (LSFs) and crosstalk ratios for each image. The line source experiments showed that the LSFs for the Tl-201 imaging window from the single Tl-201 source were very similar to those for the I-123 imaging window from the single Tl-201 source, but the LSFs for the Tl-201 imaging window from the single I-123 source had broad shapes which differed from those for the I-123 imaging window from the single I-123. To obtain accurate I-123 crosstalk images in the Tl-201 imaging window from the I-123 images in the I-123 imaging window, we designed a low-pass blurring filter. In 7 clinical I-123 MIBG studies, I-123 window images processed with this filter became very similar to the Tl-201 window image from the single I-123 source. The method proposed in this study can accurately correct the crosstalk in dual isotope studies with Tl-201 and I-123 and is easily applicable to conventional gamma camera systems with any dual energy window acquisition mode.     

Iodine-123 MIBG imaging before treatment of heart failure with carvedilol to predict improvement of left ventricular function and exercise capacity

BACKGROUND. We examined whether cardiac sympathetic imaging with iodine-123 metaiodobenzylguanidine (MIBG) would predict improvement of left ventricular (LV) function and exercise capacity in patients with heart failure after treatment with carvedilol. METHODS AND RESULTS. Eighteen patients with heart failure and 5 control subjects underwent I-123 MIBG imaging. Heart-to-mediastinum ratios at 20 minutes and 3 hours and myocardial washout rates (WR) were measured. Of the 18 patients, 11 were randomized to receive carvedilol medication, whereas the remaining 7 received a placebo. Only the carvedilol group demonstrated a significant improvement in both heart failure functional class and LV ejection fraction (EF) 1 year after the start of medication. Within the carvedilol group, MIBG WR showed a significant inverse correlation with improvement in LVEF (rho = -0.74, P =.02). The diagnostic accuracy of WR for predicting EF response to carvedilol was 91%. WR also appeared to be inversely related to the peak oxygen consumption rate (rho = -0.65, P =.08), although this did not reach statistical significance. CONCLUSION. I-123 MIBG imaging appears useful in predicting which patients with heart failure are likely to show the most improvement in LV function and exercise capacity after carvedilol treatment. Further studies in this area appear to be warranted.     

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 less than 0.01), showing a significant negative correlation with the left ventricular ejection fraction (r = -0.72 P less than 0.05). For 201Tl, 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.     

Clinical significance of I-123 MIBG myocardial scintigraphy for evaluating the severity of congestive heart failure

We studied the significance of I-123 MIBG (metaiodobenzylguanidine) myocardial scintigraphy for evaluating the severity of congestive heart failure. I-123 MIBG scintigraphy was performed in 7 patients with congestive heart failure (CHF) of NYHA class I-III (6 with dilated cardiomyopathy and 1 with Adriamycine cardiomyopathy) and in 2 normals. The SPECT and anterior planar myocardial images were obtained 15 minutes after (initial images) and 4 hours after (delayed images) an injection of I-123 MIBG (111 MBq). Compared with normals, patients with CHF demonstrated (1) low myocardial uptake and (2) rapid myocardial washout of I-123 MIBG, indicating myocardial sympathetic disarrangement. Then, quantitating these abnormalities with the heart to upper mediastinum uptake ratio (H/B) and the percent washout rate (%WR) during 4 hours, respectively, we compared these two indices with LV ejection fraction (EF) at rest measured by echocardiography and exercise capacity (max VO2 and VO2 at anaerobic threshold (AT] determined with respiratory gas exchange analysis during maximal bicycle exercise. H/B was lower and %WR was greater in patients with CHF than in normals. H/B correlated with EF (r = 0.77, p less than 0.05) and AT (r = 0.74, p less than 0.05). On the other hand, %WR significantly correlated with EF (r = 0.79, p less than 0.05), max VO2 (r = -0.74, p less than 0.05) and AT (r = -0.81, p less than 0.05). Thus, H/B and %WR were closely related to the severity of CHF. These results suggest that I-123 MIBG myocardial scintigraphy and the quantitative analysis of I-123 MIBG myocardial uptake provide useful information about the severity of CHF.     

Prognostic value of myocardial MIBG scintigraphy findings in patients with cardiomyopathy--importance of background correction for quantification of MIBG activity

OBJECTIVE: To assess the prognostic value of I-123 metaiodobenzylguanidine (MIBG) scintigraphy findings, and establish the most appropriate method for calculating myocardial MIBG activity in patients with left ventricular dysfunction due to cardiomyopathy (CM). METHODS: Predictors of cardiac death related to progressive heart failure (HF) were examined in 150 patients with CM (80 patients with idiopathic CM and 70 patients with ischemic CM). All patients underwent MIBG scintigraphy at rest and other hemodynamic studies when their clinical status was stable. MIBG scintigrams were obtained 15 minutes and 4 hours after the injection of the isotope. The parameters for quantification of myocardial MIBG activity were heart/mediastinal activity ratio (H/M) and myocardial washout rate (WR). The WR was calculated with and without background (BG) correction. RESULTS: The WR showed better correlation with plasma norepinephrine and left ventricular ejection fraction after BG correction. During a mean follow-up period of 33 +/- 9 (7 to 54) months, 12 patients died due to HF; 7 patients due to progressive HF and 5 patients due to sudden cardiac death. Cox regression analysis indicated, the H/M and the WR with and withoutBG correction, were significant predictors of cardiac death (Wald chi-squared value: H/M [ 15 min] = 9.7, H/M [4 hr] = 19.5, WR with BG correction = 29.9, WR without BG correction = 12.6). WR prognostic value was better after BG correction, and a high WR with BG correction was the only independent predictor of cardiac death (relative risk [RR] = 1.174, p < 0.0001). CONCLUSIONS: Accelerated WR is a powerful predictor of the patient's prognosis and BG correction is essential for calculating WR.     

Assessment of myocardial damage and metabolic disorder in the left ventricle in patients with mitral stenosis using 201Tl and 123I-BMIPP myocardial SPECT

This study was designed to evaluate the myocardial damage and metabolic disorder of the left ventricle in patients with mitral stenosis. We studied 15 patients with mitral stenosis. Their grade of chronic heart failure using New York Heart Association classification were class I: 5 patients, class II: 5, class III: 3, class IV: 2, respectively. The severely stenotic group (valve area < 1.5 cm2) included 6 patients, mildly stenotic group (1.5 cm2 < or = valve area < 2.5 cm2) included 9. A 111 MBq of 123I-BMIPP was intravenously injected at rest, SPECT images were obtained at 15 min and 3 hours after injection. A 111 MBq of 201Tl was intravenously injected at rest, and SPECT images were obtained at 15 min after injection. Washout rate (WR) of 123I-BMIPP from the whole left ventricle was obtained using polar maps. The concentration of norepinephrine (NE: pg/ml) in the blood at rest was measured. The mean values of pulmonary artery pressure was measured in ten patients using Swan-Ganz catheter. 123I-BMIPP myocardial SPECT and measurement of NE were reexamined in 5 patients after mitral valvuloplasty. NE values were 476 +/- 72 and 793 +/- 286 in classes I + II and III + IV, respectively. NE values was increased in the severe heart failure group (p < 0.05). NE values were 480 +/- 69 and 743 +/- 295 in the mildly and severely stenotic groups, respectively. NE value was increased in severely stenotic group (p < 0.05). Twelve patients showed normal uptake on both 201Tl and 123I-BMIPP myocardial SPECT. Three patients showed slightly reduced uptake on both 201Tl and 123I-BMIPP myocardial SPECT. WR was 27.2 +/- 4.8% and 44.3 +/- 6.7% in class I + II and class III + IV, respectively. WR was increased in severe heart failure group (p < 0.05). WR was 27.8 +/- 6.0% and 41.3 +/- 9.4% in the mildly and severely stenotic group, respectively. WR was increased in the severely stenotic group (p < 0.05). NE was correlated with WR (p < 0.001). In patients with mitral valvuloplasty, WR was 44.3 +/- 6.7% and 31.4 +/- 4.7% before and after mitral valvuloplasty, respectively. NE values were 857 +/- 266 and 574 +/- 165, respectively. Both WR and NE were decreased after mitral valvuloplasty (p < 0.01). In patients with mitral stenosis, WR was increased in the severe heart failure group and severely stenotic group without apparent myocardial damage. Myocardial metabolism in the left ventricle might be influenced by right heart failure through, for example, NE and neurohormonal factors.     

The effect of β-blocker on hamster model BIO 53.58 with dilated cardiomyopathy determined using<Superscript>123</Superscript>I-MIBG myocardial scintigraphy

OBJECTIVE: 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is currently used to evaluate cardiac sympathetic nerve function, but MIBG also has the capacity to evaluate dilated cardiomyopathy (DCM) severity and therapeutic effectiveness. In this study, we administered beta-blockers to a DCM hamster model and evaluated the effect of therapy using MIBG. We also pathologically compared the effects of myocardial fibrosis suppression. METHODS: BIO 53.58 hamsters were divided into the following five groups based on beta-blocker administration: vehicle (COT), 2 mg/kg/day carvedilol (CLT), 20 mg/kg/day (CHT) carvedilol, 4 mg/kg/day (MLT) metoprolol, 40 mg/kg/day (MHT) metoprolol. F1B hamsters were administered a vehicle (COF). Plasma catecholamine, noradrenaline (p-NADR), adrenaline (p-ADR), and dopamine (p-DOPA) were assayed, and MIBG was performed. The count ratio of the heart to the mediastinum (H/M) and left ventricle myocardial washout ratio (WR) were calculated. We then performed an autopsy and calculated the percent change in fibrotic area from myocardial sections. RESULTS: H/M of the initial image in the COT group was significantly lower at 2.4 +/- 0.2 than the 2.9 +/- 0.7 in the COF group (p < 0.05). The CLT and CHT groups had higher H/M values compared to the COT group (3.1 +/- 0.6, 3.0 +/- 0.6 versus 2.4 +/- 0.2: p < 0.05). Significant correlations were evident between the H/M of the delayed image and p-NADR and p-DOPA (p < 0.05, p < 0.01, respectively) as well as between WR and p-NADR and p-DOPA (p < 0.05). Percent change in fibrotic area was significantly lower in the beta-blocker groups than in the COT group (p < 0.05). Significant negative correlations were seen between the H/M of the delayed image and the percent change in fibrosis area. CONCLUSIONS: The delayed image H/M and WR acutely reflected cardiac disorder and sympathetic nerve function disorder in BIO 53.58 hamsters. In the carvedilol-administered groups, there was improvement compared to the initial H/M image, indicating the efficacy of the beta-blocker in DCM.     

Abnormality of the myocardial sympathetic nervous system in a patient with Becker muscular dystrophy detected with iodine-123 metaiodobenzylguanidine scintigraphy.

PURPOSE: This study was performed to determine whether I-123 metaiodobenzylguanidine (MIBG) scintigraphy can depict myocardial sympathetic nerve abnormalities in Becker muscular dystrophy. MATERIALS AND METHODS: A 34-year-old man with Becker muscular dystrophy underwent Tl-201 and I-123 MIBG scintigraphy sequentially before and 4 months after the beginning of oral administration of enalapril maleate, an angiotensin-converting enzyme inhibitor. RESULTS: Before and during treatment, stress Tl-201 scintigraphy revealed nonreversible myocardial perfusion defects in the anterior, inferoposterior, and apical walls, and I-123 MIBG scintigraphy depicted a region with decreased sympathetic nerve function or innervation. Before treatment, the I-123 MIBG heart count- mediastinum count (H:M) ratio was 2.1 and the washout rate was 21% on delayed images obtained 4 hours after the injection of I-123 MIBG, indicating hyperactivity of the sympathetic nervous system in the myocardium. During treatment, the H:M ratio was 3.0 and the washout rate was 15%. CONCLUSION: With I-123 MIBG scintigraphy it is possible to evaluate an abnormality of the myocardial sympathetic nervous system and the efficacy of administration of an angiotensin-converting enzyme inhibitor in this disease.     

Iodine-123 BMIPP scintigraphy in the evaluation of patients with heart failure

PURPOSE: To investigate whether cardiac parameters obtained by I-123 15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP, a radioactive fatty acid analogue) myocardial scintigraphy are useful as indicators of disease severity and predictors of cardiac events in congestive heart failure (CHF). MATERIAL AND METHODS: Thirty-two CHF patients (functional class: 17 in NYHA II and 15 in NYHA III at the time of this study) were compared with 18 normal control subjects. Myocardial scintigraphy was performed 15 min and 3 hours after I-123 BMIPP injection. The heart-to-mediastinum count ratio of I-123 BMIPP on the initial (H/Mi) and delayed (H/Md) images and the washout rate (WR) were calculated. RESULTS: Both H/Mi and H/Md were lower in CHF than in controls (H/Mi 1.96+/-0.18 vs. 2.30+/-0.29; H/Md 1.72+/-0.15 vs. 1.97+/-0.21; both P<0.001), but WR was higher in CHF than in controls (WR (%) 23.7+/-5.7 vs. 18.2+/-6.0, P<0.01). Both H/Mi (R = 0.42, P<0.05) and H/Md (R = 0.45, P<0.05) correlated positively with the left ventricular (LV) ejection fraction (EF), estimated by echocardiography. The WR correlated positively with the plasma B-type natriuretic peptide (BNP) level (R = 0.47, P<0.01). Kaplan-Meier analysis showed an earlier CHF progression for patients with a lower H/Mi (<1.94). CONCLUSION: Myocardial metabolic abnormality evaluated by I-123 BMIPP scintigraphy is related to the severity of CHF. Furthermore, it may be useful as a predictor for cardiac events.     

Pheochromocytoma and the normal adrenal medulla: improved visualization with I-123 MIBG scintigraphy

The radiopharmaceutical iodine 131 metaiodobenzylguanidine (I-131 MIBG) has been shown to locate pheochromocytomas scintigraphically with a false-negative rate of approximately 13%. To improve image quality and reduce the false-negative rate, I-123 was examined as a radioactive label for MIBG, as it has many advantages over I-131, including superior dosimetry and better detection efficiency. Diagnostic doses of 0.5 mCi (18.5 MBq) I-131 MIBG and 10.0 mCi (370.0 MBq) I-123 MIBG with nearly equivalent radiation dosimetries were compared in 18 patients with known or suspected pheochromocytomas. Images of superior quality were obtained with I-123 MIBG in 18 of 18 patients, and in eight cases lesions not visualized on I-131 MIBG scintigraphy were portrayed. A further advantage of I-123 MIBG is that it permits single photon emission computed tomography (SPECT). This was performed in six cases and provided additional information in three cases. The adrenal medullae were definitely visualized using I-123 scintigraphy in eight of 14 patients still possessing adrenal glands, whereas I-131 MIBG images portrayed the adrenal medulla in only one of 14 cases. Five remaining patients had multiple abdominal tumor deposits that were difficult to differentiate from normal adrenal medullae.     

The reversibility of cardiac neuronal function after removal of a pheochromocytoma: an I-123 MIBG Scintigraphic Study.

PURPOSE: Twelve patients with proved pheochromocytoma evaluated in our institution between 1991 and 1997 are described. METHODS: The patients' urinary excretion rates and their metabolites (vanylmandelic acid and metanephrines) were significantly greater than normal before surgery. Echocardiography showed normal left ventricular ejection fractions (72% +/- 8%). All of the patients underwent planar I-123 metaiodobenzylguanidine (MIBG) scintigraphy to assess cardiac neuronal uptake 4 hours after and locate a pheochromocytoma 24 hours after intravenous injection of 185 MBq (3 mCi) I-231 MIBG. Ten patients with pheochromocytoma had positive tumoral findings with I-123 MIBG scintigraphy. Twelve patients had significant impairment of cardiac neuronal uptake of MIBG, with a heart:mediastinum ratio averaging 142% +/- 18% (normal value, 230% +/- 30%, P < 0.05). Postoperative cardiac MIBG imaging was performed in all patients (at 6 +/- 3 months). RESULTS: After surgical removal of the pheochromocytoma, cardiac MIBG uptake and the heart:mediastinum uptake ratios improved significantly (197% +/- 20%, P < 0.05) in all the patients. Urinary excretion rates and metabolites returned to the normal range. However, no significant correlation was found between cardiac MIBG uptake and urinary excretion rates and metabolites after the tumors were removed. CONCLUSION: Removing a pheochromocytoma reversed cardiac neuronal function as assessed by MIBG scintigraphy.     

Relationship between thallium-201 myocardial SPECT and findings of endomyocardial biopsy specimens in dilated cardiomyopathy

The purpose of this study was to clarify which myocardial histological findings associated with dilated cardiomyopathy (DCM) are reflected in quantitative 201Tl myocardial SPECT. We obtained studied SPECT images from 21 patients with DCM 10 minutes and 2 hours after they received an injection of 111 MBq 201Tl at rest. We calculated the percent coefficient of variation of myocardial 201Tl counts [%CV(TI)], the washout rate (WR), standard deviation of WR [SD(WR)], extent score (ES) and severity score (SS). We used image analysis to measure % fibrosis, % myocytes, the ratio of fibrous tissue to myocyte tissue (F/My), myocyte size and standard deviation of myocyte size [SD(My)] in left ventricular endomyocardial biopsy specimens. The %CV(Tl) was correlated with % fibrosis and F/My. The ES and SS also correlated with F/My. The correlation between SD(WR) and SD(My) was significant. The present findings suggest that %CV(Tl), ES and SS of rest 201Tl SPECT reflect myocardial fibrosis and that the standard deviation of washout reflects the distribution of myocyte size.     

Comparison of parameters of 123I-MIBG scintigraphy for predicting prognosis in patients with dilated cardiomyopathy.

123I-metaiodobenzylguanidine (MIBG) scintigraphy has been used to predict prognosis of patients with dilated cardiomyopathy (DCM), although it is unknown which parameter of MIBG is the most useful clinically. We studied MIBG in 59 patients with DCM, and followed them up to evaluate the prognosis of DCM. Single photon emission tomography (SPET) and planar imaging were performed, both early (e) and 4 h (delayed, d) post-injection. 201Tl (TL) SPET and radionuclide-ventriculography were also investigated. The total defect score of early and delayed MIBG and 201 Tl (MIBGeDS, MIBGdDS, TLDS) was analysed visually for each SPET image. The heart to mediastinum ratio (H/M) for both the early and delayed MIBG planar images and myocardial washout rate at 4 h were analysed quantitatively. Sixteen patients died during follow-up. Cox Hazards univariate analysis selected washout rate (P < 0.0001), H/Me (P = 0.0012), H/Md (P = 0.0001) and left ventricular ejection fraction (P = 0.0004) as indices for the prediction of cardiac death. Multivariate analysis selected washout rate as the most powerful independent predictor of prognosis (P < 0.0001). Survival curves with a threshold value of 52% for washout rate were able to differentiate a negative outcome from survival (P < 0.0001). TLDS, MIBGeDS and MIBGdDS were not useful in the prediction of prognosis. The washout rate of MIBG is the most potent predictor of cardiac death and is considered clinically useful.     

Diagnosis and treatment of neuroblastoma using metaiodobenzylguanidine

Neuroblastoma is a lethal and not uncommon tumor in childhood. Early detection and display of the spread of the tumor is highly desirable for proper treatment. Nine children suspected of having neuroblastomas were examined by I-131 metaiodobenzylguanidine (I-131 MIBG) imaging. In two recent studies I-123 metaiodobenzylguanidine (I-123 MIBG) was used. A primary adrenal neuroblastoma was correctly identified in three cases. In two patients additional tumor sites were found. In one patient, who was in complete remission, no pathologic accumulation of I-131 MIBG was found. I-131 MIBG images were also normal in four patients with other types of neoplastic diseases. A boy with multiple metastases was treated with 100 mCi of I-131 MIBG. He developed transient gastrointestinal illness and there was no regression of the tumor deposits. In one girl with a large adrenal neuroblastoma high uptake of I-131 MIBG was observed. She received two therapy doses of I-131 MIBG (35 mCi and 75 mCi) with curative intention giving a total absorbed dose in the tumor of approximately 76 Gy. In spite of high retention of radioactivity in the tumor, regression did not occur, but her general condition was improved. In the present study, images of superior quality were obtained with I-123 MIBG imaging. It is concluded that imaging using I-131 MIBG or I-123 MIBG should be used in both the initial evaluation and the follow-up of children with neuroblastoma.     

Scintigraphic assessment of patients with electrocardiographic left ventricular hypertrophy with ST-T changes without apparent cause

PURPOSE: Some patients who show electrocardiographic left ventricular hypertrophy with ST-T changes (ECG-LVH) are difficult to evaluate using routine examinations. To clarify the pathologic process in these patients, the authors performed several scintigraphic examinations. MATERIALS AND METHODS: Twenty-nine patients with ECG-LVH, without apparent cause, such as left ventricular (LV) systolic overloading or increased LV mass, were examined by myocardial I-123 MIBG imaging, I-123 BMIPP imaging, and exercise-induced stress perfusion imaging. In addition to the visual assessment of each image, we calculated global and regional myocardial washout of I-123 MIBG (%washout). The LV was assessed using conventional echocardiography. RESULTS: Visually observed abnormalities were located exclusively at the LV apex with all imaging methods and were detected in 76%, 52%, and 17% of patients by I-123 MIBG, I-123 BMIPP, and perfusion imaging, respectively. A follow-up study revealed that the apical defects of I-123 MIBG were subsequently followed by defects of I-123 BMIPP and then perfusion abnormalities. In patients with an apical defect revealed by I-123 MIBG imaging, apical %washout was high. In nine patients who underwent myocardial biopsy, myocardial disarray was observed at the apical regions. CONCLUSIONS: In many patients with ECG-LVH without apparent cause, sympathetic abnormalities are observed at the apex, similar to pathologic changes in hypertrophic cardiomyopathy. These abnormalities may lead to changes in fatty acid metabolism and perfusion.     

Cilnidipine as an agent to lower blood pressure without sympathetic nervous activation as demonstrated by iodine-123 metaiodobenzylguanidine imaging in rat hearts

BACKGROUND: Administration of short-acting antihypertensive agents to patients with ischemic heart disease results in increased sympathetic nervous activity and is associated with worsened outcomes. Cilnidipine is an agent which blocks not only L-type calcium channels at the smooth muscle in the artery, but also N-type calcium channels at the presynaptic terminal. The goal of the present study was to determine the effect of cilnidipine on sympathetic nervous activity as on agent which blocks both L-type and N-type calcium channels at the presynaptic terminal, on sympathetic nervous activity in an experimental rat model using iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging. METHODS: Fourteen-week-old Wistar-Kyoto rats were divided into 3 separate groups: CTR group (control: distilled water administered), Nif group (nifedipine administered), or Cil group (cilnidipine administered). Agents were administered via a stomach tube, followed by injection of MIBG via the femoral vein. Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff plethysmography just prior to administration of antihypertensive drugs and 150 minutes later. Initial imaging (Ce) and delayed imaging (Cd) were defined as the sum of density counts in the region of interest created by adjusting to myocardial edge, and were corrected for both physical decay and weight. The myocardial washout rate (WR) was defined as the percent change in the count density from the initial to delayed images. RESULTS: Significant decreases in SBP were seen in the Nif group (from 132 +/- 3 mmHg to 85 +/- 5 mmHg, p < 0.0001) and the Cil group (from 128 +/- 4 mmHg to 92 +/- 7 mmHg, p = 0.0008), whereas no significant change in SBP was noted in the CTR group (from 123 +/- 5 mmHg to 127 +/- 3 mmHg). HR significantly increased in the Nif group (from 290 +/- 12/min to 378 +/- 14/min, p < 0.0001) but not in the CTR (from 278 +/- 3/min to 300 +/- 6/min) or Cil (from 291 +/- 6/min to 303 +/- 5/min) groups. WR was significantly greater in the Nif group (64.7 +/- 0.5%) when compared to the CTR (56.4 +/- 1.2%, p = 0.0031) or the Cil (55.4 +/- 2.2%, p = 0.0016) groups. CONCLUSION: In contrast to nifedipine, administration of cilnidipine did not result in increased myocardial sympathetic nervous activation.     

Myocardial adrenergic derangement due to myocardial ischemia: decreased myocardial uptake of I-123 metaiodobenzylguanidine after PTCA in a patient with effort angina

Regional denervation of adrenergic nerves has been clinically demonstrated in patients with myocardial infarction using I-123 metaiodobenzylguanidine (MIBG) scintigraphy. However, it is not clarified whether adrenergic denervation can be induced by prolonged myocardial ischemia as well as by myocardial infarction. This case with effort angina had 99% stenosis of right coronary artery and showed perfusion defects at inferior myocardial regions in the exercise thallium-201 study. However, inferior wall motion estimated by echocardiography and left ventriculography was normal indicating the absence of myocardial infarction. After percutaneous transluminal coronary angioplasty for the stenosis, I-123 metaiodobenzylguanidine (MIBG) and thallium-201 (Tl-201) myocardial scintigraphies were done to estimate the therapeutic effect of PTCA. Although the Tl-201 study during exercise showed normal findings indicating the success of PTCA, marked defects was detected at inferior myocardial regions in the I-123 MIBG studies just after and 4 hours after an intravenous injection of I-123 MIBG. These results suggest that adrenergic derangement may be induced by prolonged myocardial ischemia and may persist for periods even though myocardial perfusion is normalized.