HIV Dementia with a Decreased Cardiac 123I-metaiodobenzylguanidine Uptake Masquerading as Dementia with Lewy Bodies.

Cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy is a promising biomarker for dementia with Lewy bodies (DLB). However, we experienced a patient with cognitive decline, parkinsonism, and a decreased MIBG uptake who turned out to have HIV dementia. Normal dopamine transporter single-photon emission computed tomography reduced the possibility of comorbid Lewy body pathology causing the patient' s parkinsonism. The decreased MIBG uptake was most likely due to postganglionic sympathetic nerve denervation, which can also be caused by HIV. This case further emphasizes the importance of excluding other causes of autonomic neuropathy, including HIV infection, before interpreting MIBG scans.

Prognostic value of 123I-metaiodobenzylguanidine in patients with various heart diseases.

OBJECTIVE: It has been reported that (123)I-metaiodobenzylguanidine (MIBG) scintigraphy can predict the poor prognosis in patients with dilated cardiomyopathy (DCM). However, the prognostic significance of MIBG is still unknown in patients with other heart diseases. In this study, we compared the prognosis and MIBG findings in various heart diseases. METHODS: Consecutive 565 patients undergoing MIBG scintigraphy were enrolled (392 men, 52 +/- 16 years). Indications were that 127 had ischemic heart disease (IHD), 120 DCM, 101 hypertrophic cardiomyopathy (HCM), 21 hypertensive heart disease (HHD), 58 volume-load valvular disease (VVD), 38 pressure-load valvular disease (PVD), and 101 ventricular tachycardia or fibrillation (VTF). Heart-to-mediastinum ratio (H/M) and washout rate (WR) of MIBG were evaluated. Cardiac events were defined as sudden cardiac death, heart failure, and acute ischemic event (follow-up, 22.7 +/- 17.0 months). RESULTS: A total of 106 cardiac events including 40 cardiac deaths occurred. Cox hazard model analysis showed that in the IHD, HCM, and DCM groups, H/M and WR were associated with cardiac death, but not in the HHD, PVD, VVD, or VTF groups. Only death and congestive heart failure (CHF) episodes were related to H/M and WR. On the other hand, fatal arrhythmia, myocardial infarction, or angina pectoris were not related to H/M and WR. The data indicated that WR or H/M may predict death and CHF but does not predict fatal arrhythmia or acute ischemic event. CONCLUSIONS: MIBG WR and H/M were associated with heart failure, sudden death, and cardiac death events, and were useful to predict the prognosis in DCM, HCM, and IHD. In contrast, fatal arrhythmia events were not associated with MIBG indices, and thus it does not appear to be useful in predicting cardiac events in patients with VTF.

Human megakaryocytes cultured in vitro accumulate serotonin but not meta-iodobenzylguanidine whereas platelets concentrate both.

OBJECTIVE: Thrombocytopenia is the major toxicity of radio-iodinated meta-iodobenzylguanidine (MIBG) therapy in patients with recurrent neuroblastoma. MIBG is taken up in platelets via the serotonin transporter. Given the delayed appearance and long duration of the thrombocytopenia, it seems likely that the precursor megakaryocytes are the primary targets of [131I]MIBG radiotoxicity. MATERIALS AND METHODS: We investigated MIBG and serotonin uptake in cultured human megakaryocytes grown in vitro from CD34(+) cells obtained from bone marrow. RESULTS: With radio-iodinated MIBG, cell-associated radioactivity was negligible, even after prolonged incubations for up to 16 hours. In contrast, after 4 or 16 hours with 10(-8) M [3H]serotonin, 6% or 14% of the added substrate was accumulated in the megakaryocytes. This uptake approached saturation above 10(-7) M and was reduced greater than 90% by coincubation by imipramine. This indicates specific uptake, which was confirmed by fluvoxamine and citalopram. The serotonin reuptake inhibitors fluvoxamine (0.3 nM) and citalopram (1 nM) effectively reduced serotonin uptake to 44% +/- 3% and 30% +/- 9% of the controls, respectively. CONCLUSIONS: Megakaryocytes efficiently retain serotonin in storage granules, as concluded from the consistent reductive effect of tetrabenazine on uptake, retention, and localization (micro-autoradiographic) of serotonin. Thus, serotonin, but not MIBG, is taken up by cultured megakaryocytes.

Bioanalysis of m-iodobenzylguanidine in plasma by high-performance liquid chromatography after derivatization with benzoin.

A sensitive chromatographic assay has been developed for m-iodobenzylguanidine (MIBG) in human plasma based on the derivatization with benzoin. MIBG is first isolated from plasma using solid-phase extraction on a cyanopropyl-modified silica phase. After evaporation of the eluate, a fluorescent derivative is formed using benzoin. The derivative is analysed by reversed-phase liquid chromatography using a mixture 60% (v/v) acetonitrile, 30% (v/v) water and 10% (v/v) of the 0.5 M Tris buffer (pH 8.0) as the eluent and fluorescence detection at 320 nm for excitation and 435 nm for emission, respectively. In the evaluated concentration range (2-200 ng/ml) precisions < or = 10% and accuracies in between 90 and 100% have been found, with 2 ng/ml being the lower limit of quantification using a 0.5-ml plasma sample volume. The assay can also be used without the internal standard benzylguanidine. The assay was successfully used to obtain a pharmacokinetic curve of MIBG.

Washout of I-123 meta-iodobenzylguanidine for assessing cardiac sympathetic activity with progression of hypertension in Dahl salt-sensitive rats.

BACKGROUND: To evaluate cardiac sympathetic activity, a simple method should be developed to replace such complex methods as the spillover rate of tritiated norepinephrine (3H-norepinephrine) or microneurography of sympathetic nerve activity. The goal of this study is to evaluate cardiac sympathetic activities by analyzing the washout of I-123 meta-iodobenzylguanidine (123I-MIBG), a radiolabeled norepinephrine analogue, in Dahl salt-sensitive (DS) rats as it relates to the progression of hypertension. METHODS AND RESULTS: Dahl salt-resistant (DR) rats and DS rats were fed an 8 % salt diet starting at age 5 weeks. Marked hypertension and cardiac hypertrophy developed in the DS rats, whereas DR rats remained normotensive. Then the time-activity curves of 123I-MIBG from 15 to 200 minutes were obtained from both DS and DR strains at ages 8, 11, and 13 weeks using dynamic scintigraphic analysis. We also examined the nonneuronal washout of 123I-MIBG using dynamic scintigraphic studies in desipramine pretreated normal rats. In the preliminary study with desipramine pretreatment, the majority of the nonneuronal 123I-MIBG washout occurred by 90 minutes after injection. Therefore the late-phase washout in the control rats was found to reflect the neuronal washout. We then applied exponential curve fitting to the time activity curves acquired in the 90- to 200-minute period after 123I-MIBG injection in both DR and DS rats. When we compared the coefficients of these washout curves in the DS and DR rats as an index of cardiac sympathetic activities, the coefficient values remained high during all stages in DS rats, whereas they decreased with age in DR rats. CONCLUSION: Measurement of late-phase 123I-MIBG washout may be a useful tool for assessing the change in sympathetic activity in the progression of hypertension without the influence of extraneuronal washout of 123I-MIBG and left ventricular hypertrophy.