Adrenal ganglioneuroma with nodal metastases on 123I-MIBG SPECT/CT and 18F-FDG PET/CT.

Ganglioneuroma is a well-differentiated tumor originating from neural crest cells of the sympathetic nervous system. Although benign, a few cases have been reported that ganglioneuroma can metastasize to other sites. We report a case of adrenal ganglioneuroma with para-aortic nodal metastases with low FDG and MIBG uptake. In order to avoid unnecessary wide excision or aggressive medication, it is important to consider the possibility of ganglioneuroma preoperatively even if with metastases.

Relationships between neuroimaging biomarkers and glymphatic-system activity in dementia with Lewy bodies.

Alpha-synuclein deposits in the brain have been suspected to cause Parkinson's disease and dementia with Lewy bodies (DLB). It was recently revealed that the glymphatic system is largely responsible for the removal of alpha-synuclein. We investigated changes in the glymphatic system's activity by determining the DTI­ALPS (diffusion tensor image analysis along the perivascular space) index in DLB patients. Twenty-six patients with DLB and 43 healthy subjects underwent diffusion tensor imaging (DTI) scanning at our hospital during the period April 2013 to March 2023. We retrospectively computed each subject's DTI­ALPS index to evaluate his/her glymphatic-system activity and then analyzed the relationships between the subjects' DTI­ALPS index data and their DLB neuroimaging biomarker values. A significant reduction of the DTI­ALPS index was observed in the patients with DLB compared to the healthy subjects. Significant positive correlations were also detected in the DLB group between the DTI­ALPS index and the regional gray matter volume in the left insula and between the index and the specific binding ratio of 123I-N-ω-fluoropropyl-2ß-carboxymethoxy-3ß-(4-iodophenyl)nortropane ([123I]-FP-CIT). These results indicate that (i) the DTI­ALPS index is a good biomarker of the progression of DLB, and (ii) this index might be effective to distinguish DLB from other neurocognitive disorders.

Serum phosphorus levels associated with nigrostriatal dopaminergic deficits in drug-naïve Parkinson's disease.

INTRODUCTION: A major component of Lewy bodies is phosphorylated α-synuclein. This post-translational modification of α-synuclein, phosphorylation, may consume a great amount of serum phosphorus. We aimed to investigate serum phosphorus levels and their associations with clinical phenotype and the degeneration of cardiac sympathetic and nigrostriatal dopaminergic neurons in patients with Parkinson's disease (PD). MATERIALS AND METHODS: We examined serum phosphorus levels in 127 participants (drug-naïve PD, 97; age- and sex-matched controls, 30). Associations of serum phosphorus levels with clinical features, heart-to-mediastinum (H/M) ratio on cardiac 123I-metaiodobenzylguanidine scintigraphy and striatal specific binding ratio of 123I-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) were examined. RESULTS: Serum phosphorus levels were 3.4 ± 0.5 mg/dL in patients with PD and were not different from those in controls after controlling for age and sex (p = 0.850). Serum phosphorus levels were significantly lower in patients with PD and decreased H/M ratio than in those with PD and normal H/M ratio (3.3 ± 0.4 mg/dL vs. 3.6 ± 0.5 mg/dL, p = 0.003). Lower serum phosphorus levels were significantly associated with more severe degeneration of nigrostriatal dopaminergic neurons in patients with PD and decreased H/M ratio. However, this association was not observed in patients with PD and normal H/M ratio. CONCLUSIONS: Serum phosphorus levels and their association with nigrostriatal dopaminergic degeneration are different between patients with decreased H/M ratio and those with normal H/M ratio. Serum phosphorus levels may reflect the degree of nigrostriatal dopaminergic degeneration in patients with decreased H/M ratio, namely, Body-First PD.

Predictors of appropriate therapies delivered by the implantable cardioverter-defibrillator in patients with coronary artery disease during long-term period.

This prospective study aimed to investigate the ability of cardiac autonomic nervous system (CANS) activity assessment to predict appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease (CAD) during long-term follow-up period. We enrolled patients with CAD and ICD implantation indications that included both secondary and primary prevention of sudden cardiac death. Before ICD implantation CANS was assessed by using heart rate variability (HRV), myocardium scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG) and erythrocyte membranes ß-adrenoreactivity (EMA). The study's primary endpoint was the documentation of appropriate ICD therapy. Of 45 (100.0%) patients, 15 (33.3%) had appropriate ICD therapy during 36 months follow-up period. Patients with appropriate ICD therapy were likely to have a higher summed 123I-MIBG score delayed (p < 0.001) and lower 123I-MIBG washout rate (p = 0.008) indicators. These parameters were independently associated with endpoint in univariable and multivariable logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.933 (95% confidence interval 0.817-0.986; sensitivity 100.00%; specificity 93.33%). Combined CANS activity assessment is useful in prediction of appropriate ICD therapy in patients with CAD during long-term follow-up period after device implantation.

Reduced cardiac 123I-MIBG uptake is a robust biomarker of Lewy body disease in isolated rapid eye movement sleep behaviour disorder.

Cardiac 123I-MIBG scintigraphy is used to assess the function of postganglionic presynaptic cardiac sympathetic nerve endings. 123I-MIBG cardiac uptake is markedly reduced in patients with isolated rapid eye movement sleep behaviour disorder, similar to Parkinson's disease and dementia with Lewy bodies. As a result, it can be used as an early biomarker of isolated rapid eye movement sleep behaviour disorder. Most patients with isolated rapid eye movement sleep behaviour disorder develop synucleinopathies: Parkinson's disease, dementia with Lewy bodies or multiple system atrophy. We aimed to investigate whether cardiac postganglionic denervation is present in patients with isolated rapid eye movement sleep behaviour disorder, as well as its possible usefulness as a marker for Lewy body disease status. This retrospective cohort study examined 306 patients (236 men and 70 women; mean age: 68.2 years; age range: 43-87 years) with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder who were followed for 1-3 months and underwent 123I-MIBG scintigraphy. We retrospectively analysed data from 306 patients with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder, and their longitudinal outcomes were documented at two centres. Among isolated rapid eye movement sleep behaviour disorder patients, reduced 123I-MIBG uptake was observed in the early and delayed images in 84.4 and 93.4% of patients, respectively, whereas 88.6% of the patients had a high washout rate. This large Japanese two-cohort study (n = 306) found that 91 patients (29.7%) developed an overt synucleinopathy (51 Parkinson's disease, 35 dementia with Lewy bodies, 4 multiple system atrophy, and 1 cerebellar ataxia) during a mean follow-up duration of 4.72 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.4% at 5 years, 41.4% at 8 years and 52.5% at 10 years. On the other hand, among patients with heart-to-mediastinum ratio < 2.2 in the delayed images (n = 286), 85 (29.7%) developed Parkinson's disease or dementia with Lewy bodies during a mean follow-up duration of 4.71 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.6% at 5 years, 42.0% at 8 years and 51.0% at 10 years. Among the 33 patients who underwent repeat 123I-MIBG scintigraphy, there was a progressive decline in uptake over the next 4.2 years, with patients exhibiting reduced uptake progressing to Parkinson's disease or dementia with Lewy bodies. In contrast, patients without decreased 123I-MIBG uptake progressed to multiple system atrophy. Reduced cardiac 123I-MIBG uptake was detected in over 90% of isolated rapid eye movement sleep behaviour disorder patients, with progression to Parkinson's disease or dementia with Lewy bodies, rather than multiple system atrophy, over time. Reduced 123I-MIBG uptake is a robust maker for Lewy body disease among isolated rapid eye movement sleep behaviour disorder patients.

Pheochromocytoma With High Adrenocorticotropic Hormone Production Capacity Without Pigmentation and Cushingoid Symptoms: A Case Report With a Literature Review.

Pheochromocytoma or paraganglioma (PPGL) originating from chromaffin cells can produce diverse hormones in addition to catecholamines, including adrenocorticotropic hormone (ACTH). In pheochromocytoma, high levels of ACTH might not result in pigmentation as typically observed in Addison's disease, and patients might not exhibit the symptoms of Cushing's syndrome, despite ACTH-dependent hypercortisolism. A 63-year-old male patient with hypertension was admitted to our facility, and computed tomography (CT) revealed a large right adrenal tumor. Despite high plasma ACTH (700-1300 pg/mL) and serum cortisol (90-100 µg/dL) levels, no physical pigmentation or Cushingoid symptoms were observed. Urinary metanephrine and normetanephrine levels reached as high as 16.0 mg and 3.2 mg, respectively. 123I-metaiodobenzylguanidine (MIBG) scintigraphy was negative. Low-dose dexamethasone paradoxically increased ACTH and cortisol levels, indicating the potential positive feedback regulation of both hormones by glucocorticoids. The patient was diagnosed with an ACTH-producing pheochromocytoma and underwent successful laparoscopic surgery to remove the adrenal tumor under the intravenous administration of a high-dose α-blocker and hydrocortisone. The levels of ACTH, cortisol, and urinary metanephrine/normetanephrine returned close to normal after tumor removal. We report a rare case of pheochromocytoma with extremely high ACTH/cortisol production but without pigmentation or Cushingoid symptoms. We also reviewed previous reports of ACTH-producing PPGL regarding the paradoxical regulation of ACTH/cortisol by glucocorticoids, pigmentation, Cushingoid symptoms, and negativity of 123I-MIBG scintigraphy.

Correlation with sympathetic skin response, 123I-MIBG scintigraphy, and 123I-FP-CIT SPECT in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD), and other parkinsonian syndromes are known to cause striatonigral dopaminergic system dysfunction and autonomic disturbances, including the vasomotor and sudomotor nervous systems. The detection of 123I-FP-CIT SPECT (DaT scan) imaging and autonomic dysfunction helps differentiate PD from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). The sympathetic skin response (SSR) is a simple, non-invasive electrophysiological test that assesses the sympathetic sudomotor nervous system. It is reported that the SSR is impaired in patients with PD, MSA, and PSP. OBJECTIVE: To study the relationship between SSR, 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy and DaT scan imaging parameters in patients with PD, MSA, and PSP. METHODS: The study included 62, 25, and 19 patients with PD, MSA, and PSP, respectively. The SSR, MIBG cardiac scintigraphy, and DaT scan imaging were examined. The amplitude and latency of the SSR were measured in all limbs and were compared with the results of MIBG cardiac scintigraphy and DAT scan imaging. RESULTS: The SSR amplitudes were lower than reported normal subjects' reference values in PD, MSA, and PSP. The SSR amplitude only correlated with MIBG cardiac scintigraphy and DaT scan imaging parameters in PD. Multiple regression analyses also showed a significant relationship between the amplitudes of SSR and DaT scan imaging in PD. CONCLUSION: Unlike MSA, and PSP, the sudomotor nervous system is parallelly involved with cardiac sympathetic and central dopaminergic dysfunction from the early stage of PD.

Estimating motor progression trajectory pursuant to temporal dynamic status of cardiac denervation in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a multifaceted disease that encompasses diverse clinical phenotypes. The diversity of PD could be subtyped based on the temporal dynamic status of cardiac sympathetic innervation; (1) initially, denervated myocardium (peripheral nervous system-predominant; PNS-predominant), (2) preserved myocardium (central nervous system-predominant; CNS-predominant), and (3) preserved myocardium who developed cardiac sympathetic denervation (CSD) on the subsequent imaging (Converter; delayed cardiac denervation). This study assessed how the cardiac denervation could reflect the pathobiology. We investigated whether this phenotyping could help predict the motor progression trajectory of PD. METHODS: Cardiac sympathetic innervation was evaluated using initial and sequential 123I-meta-iodobenzylguanidine myocardial scintigraphy and patients were stratified into three groups as above. Motor severity and progression were evaluated in each patient. The association between subtypes and dopaminergic nigrostriatal degeneration was analyzed. The influence of cardiac denervation on motor progression was also investigated. RESULTS: Among the enrolled 195 patients, 144 PD subjects were defined as PNS-predominant, 16 as Converter, and 35 as CNS-predominant. The most severe nigrostriatal degeneration was observed in the PNS-predominant group and the dopaminergic degeneration was the most asymmetric in the CNS-predominant group. Positive linear trends of nigrostriatal degeneration and its asymmetric degeneration of striatum and globus pallidus were found across the patterns of cardiac sympathetic innervation (PNS-predominant vs. Converter vs. CNS-predominant). It indicated an increasing degree of asymmetric degeneration among the groups. A longitudinal estimation of motor progression revealed distinct cardiac denervation trajectories for each subtype. CONCLUSIONS: These results implicated that the subtypes of CSD might indicate a predominant origin and spreading pattern of pathobiology.

Effectiveness of 18F-FDG PET/CT in finding lung metastasis from a retroperitoneal paraganglioma.

A 50-year-old woman was diagnosed with iron deficiency anemia on general medical examination. Further, contrast-enhanced abdominal CT and magnetic resonance imaging revealed a large hypervascular mass with internal degeneration and necrosis in the retroperitoneal space. She was referred to our hospital for further evaluation and treatment. Because the paraganglioma was most likely as the imaging diagnosis, 123I-MIBG scintigraphy was performed. It revealed the marked abnormal accumulation in the retroperitoneal lesion indicating the paraganglioma and no other abnormal accumulation was noted. Several plasma catecholamines and their urinary metabolites were normal. On the subsequent 18F-FDG PET/CT, high FDG uptake was found in the retroperitoneal lesion (SUVmax=38). FDG uptake was also found in a small nodule at the base of the lower lobe of the right lung (SUVmax= 9.8). Contrast-enhanced imaging revealed a hypervascular nodule at the base of the right lung, suggesting pulmonary metastasis of a paraganglioma. The abdominal lesion and right lung nodule were excised, and retroperitoneal paraganglioma and pulmonary metastasis were diagnosed based on the pathology findings. In this case, 18F-FDG PET/CT was useful in the search for paraganglioma metastasis. We report a relationship between 123I-MIBG accumulation and 18F-FDG uptake in paraganglioma and review the relevant literature.

Cardiac sympathetic "morbidity" might reflect the neurobiology of early Parkinson's disease.

BACKGROUND: An appropriate extracranial biomarker that delineates endophenotypes of Parkinson's disease (PD) at an early stage and reflects the neurodegenerative process is lacking. An evaluation of myocardial sympathetic nerve terminals could be a good candidate. This study aimed to explore subtypes of PD patients that showed cardiac catecholaminergic vesicular defect and their characteristics. METHODS: This study included 122 early drug-naïve PD patients who were followed for approximately 4-5 years. All patients were examined with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane positron-emission tomography and 123I-meta-iodobenzylguanidine myocardial scintigraphy. Cardiac scans were reexamined two or three times. Patients were subgrouped into the sympathetic denervated group at the initial scan, those without evidence of denervated myocardium in the first and subsequent scans, and the converters whose myocardium was initially normal but became impaired in the subsequent scans. Cognition in 99 patients was initially assessed with neuropsychological tests. Any associations between cardiac denervation subtypes and presynaptic dopamine transporter densities were investigated. Cognitive status relevant to cardiac sympathetic denervation status was evaluated. RESULTS: This study found that cross-sectional comparisons of presynaptic monoamine transporter availability with a predefined order of cardiac denervation groups revealed parallel degeneration. A quadratic correlation between cardiac catecholamine capacity and cognition was observed. This association was interpreted to reflect the early neurobiology of PD. CONCLUSION: An observed cardiac catecholaminergic gradient was to mirror the central neurobiology of early PD.

Comparison of Taiwanese and European Calibration Factors for Heart-to-Mediastinum Ratio in Multicenter 123I-mIBG Phantom Studies.

Background: Cross-calibration of 123I-labeled meta-iodobenzylguanidine (mIBG) myocardial-derived indices is essential to extrapolate findings from several clinical centers. Here, we conducted a phantom study to generate conversion coefficients for the calibration of heart-to-mediastinum ratios and compare them between Taiwan and Europe. Methods: We used an acrylic phantom dedicated to 123I-mIBG planar imaging to calculate the conversion coefficients of 136 phantom images derived from 36 Taiwanese institutions. A European phantom image database including 191 images from 27 institutions was used. Conversion coefficients were categorized into five collimator types: low-energy (LE) high-resolution (LEHR), LE general-purpose (LEGP), extended LEGP (ELEGP), medium-energy (ME) GP (MEGP), and ME low-penetration (MELP) collimators. Results: The conversion coefficients were 0.53 ± 0.039, 0.59 ± 0.032, 0.79 ± 0.032, 0.96 ± 0.038, and 0.99 ± 0.050 for LEHR, LEGP, ELEGP, MEGP, and MELP collimators, respectively. The Taiwanese and European conversion coefficients for the LEHR, LEGP, and MELP collimators did not significantly differ. The coefficient of variation was slightly higher for the Taiwanese than the European conversion coefficients (3.7%-7.5% vs. 2.3%-5.6%). Conclusions: We calculated conversion coefficients for various types of collimators used in Taiwan using a 123I-mIBG phantom. In general, the Taiwanese and European conversion coefficients were comparable. These findings further corroborated and highlighted the need for 123I-mIBG standardization using the phantom-determined conversion coefficients.

Role of Functional Neuroimaging with 123I-MIBG and 123I-FP-CIT in De Novo Parkinson's Disease: A Multicenter Study.

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder, with incidence and prevalence rates of 8-18 per 100,000 people per year and 0.3-1%, respectively. As parkinsonian symptoms do not appear until approximately 50-60% of the nigral DA-releasing neurons have been lost, the impact of routine structural imaging findings is minimal at early stages, making Parkinson's disease an ideal condition for the application of functional imaging techniques. The aim of this multicenter study is to assess whether 123I-FP-CIT (DAT-SPECT), 123I-MIBG (mIBG-scintigraphy) or an association of both exams presents the highest diagnostic accuracy in de novo PD patients. METHODS: 288 consecutive patients with suspected diagnoses of Parkinson's disease or non- Parkinson's disease syndromes were analyzed in the present Italian multicenter retrospective study. All subjects were de novo, drug-naive patients and met the inclusion criteria of having undergone both DAT-SPECT and mIBG-scintigraphy within one month of each other. RESULTS: The univariate analysis including age and both mIBG-SPECT and DAT-SPECT parameters showed that the only significant values for predicting Parkinson's disease in our population were eH/M, lH/M, ESS and LSS obtained from mIBG-scintigraphy (p < 0.001). CONCLUSIONS: mIBG-scintigraphy shows higher diagnostic accuracy in de novo Parkinson's disease patients than DAT-SPECT, so given the superiority of the MIBG study, the combined use of both exams does not appear to be mandatory in the early phase of Parkinson's disease.

Cardiac sympathetic activity and relationship to cardiac events and left ventricular reverse remodeling in patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: Delayed heart-to-mediastinum ratio (HMR) has been associated with catecholamine levels and contractile reserve in dilated cardiomyopathy (DCM); however, there is scant evidence regarding the association between cardiac sympathetic activity and left ventricular reverse remodeling (LV-RR). We calculated the 123I-metaiodobenzylguanidine (123I-mIBG) HMR and washout rate (WR) in patients with DCM and investigated their associations with LV-RR. METHODS: From April 2003 to January 2020, in 120 patients with DCM who underwent 123I-mIBG scintigraphy. 66 patients undergoing follow-up echo and taking a beta-blocker from baseline were examined the relationship between 123I-mIBG and LV-RR. After that, this prognostic value for composite cardiac events was evaluated in the entire 120 patients. RESULTS: In LV-RR analysis, patients were 50.4 ± 12.2 years, with a mean left ventricular ejection fraction of 28.6%. Of 66 patients, 28 (42.4%) achieved LV-RR. Multiple logistic regression analysis of LV-RR revealed that not delayed HMR but the WR (cutoff value: 13.5%) was an independent predictor of LV-RR (odds ratio 6.514, p = 0.002). In the analysis for composite cardiac events, even though WR itself does not have the prognostic capacity, Kaplan-Meier survival curves divided by the cutoff value (delayed HMR = 2.0, WR = 13.5) showed that delayed HMR and WR values enabled the stratification of high-risk patients (log-rank p < 0.001). CONCLUSIONS: The 123I-mIBG WR was associated with the prevalence of LV-RR in patients taking 100% of beta-blockers and 98.5% of renin-angiotensin system inhibitors. Reflecting the contractile reserve, the combined assessment of the delayed HMR and WR could be used to further precisely stratify the patients with DCM.

68Ga-DOTATATE PET in Restaging and Response to Therapy in Neuroblastoma: A Case Series and a Mini Review.

68Ga-DOTATATE PET/CT is widely used for the evaluation of neuroendocrine tumors. Some reports exist on its use in the management of neuroblastoma. Building on the prior reports as well as our previous experience in using this technique for initial staging, we propose to describe its practical benefits in restaging and response to therapy. We describe different aspects including supply logistics, preparation, spatial resolution, and other practical applications. Methods: We reviewed the medical records for 8 patients who were evaluated with 68Ga-DOTATATE PET/CT at our institution over 2 y. A note was made of the patient and disease characteristics and the indication for PET imaging, and the results were retrospectively analyzed for feasibility, logistics, radiation exposure, and utility in answering the clinical question. Results: Eight children (5 girls and 3 boys; age range, 4-60 mo; median age, 30 mo) diagnosed with neuroblastoma were imaged with 68Ga-DOTATATE PET/CT and 5 with 123I-metaiodobenzylguanidine (123I-MIBG) SPECT/CT over 2 y. Three 68Ga-DOTATATE PET scans were done for staging, 10 for response evaluation, and 2 for restaging. 68Ga-DOTATATE PET accurately identified neuroblastoma lesions suspected or seen on anatomic imaging. It has been shown to be more specific and more sensitive than 123I-MIBG and at times also MRI. It had better spatial and contrast resolution than 123I-MIBG. 68Ga-DOTATATE PET was better than 123I-MIBG SPECT/CT, CT, and MRI in the detection of early progression and viable tumor delineation for response assessment, as well as in target volume definition for external-beam radiotherapy and proton-beam radiotherapy. 68Ga-DOTATATE PET was also better at assessing bony and bone marrow disease changes with time. Conclusion: 68Ga-DOTATATE PET/CT offers added value and a superior edge to other imaging modalities in restaging and response assessment in neuroblastoma patients. Further multicenter evaluations in larger cohorts are needed.

Optimal Protocol and Clinical Usefulness of 123I-MIBG Cardiac Scintigraphy for Differentiation of Parkinson's Disease and Dementia with Lewy Body from Non-Parkinson's Diseases.

Purpose: 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy was a useful imaging modality for the diagnosis of Parkinson's disease, but its diagnostic performances were variably reported. This retrospective study compared the diagnostic performances and investigated the optimal imaging protocol of 123I-MIBG cardiac scintigraphy at various imaging time points in patients suspected of Parkinson's disease in clinical practice. Methods: In patients suspected of Parkinson's disease, clinical records, autonomic function tests, and 123I-MIBG cardiac scintigraphy were retrospectively reviewed. Semi-quantitative parameters such as heart-to-mediastinum ratio (HMR) and washout rate (WR) were calculated and compared at 15 min, 1 h, 2 h, 3 h, and 4 h post-injection (p.i.). of 123I-MIBG cardiac scintigraphy. Group A consisted of Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy body (DLB), and group B consisted of non-Parkinson's diseases such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), drug-induced parkinsonism (DIP), essential tremor (ET), Parkinson-plus syndrome (PPS), and unspecified secondary parkinsonism (NA). The diagnostic performances of HMR and WR were compared for differentiation of group A from group B, and their clinical usefulness and optimal imaging time points were explored. Results: Seventy-eight patients were included in group A (67 PD, 7 PDD, 4 DLB), and 18 patients were included in group B (5 MSA, 3 PSP, 2 DIP, 2 ET, 1 PPS, and 1 NA). Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value of HMR and WR were maximized at 4 h p.i., (82.1%, 85.7%, 82.6%, 97.0%, and 46.2%; cutoff threshold < 1.717; area under curve 0.8086) and at the time interval between 1 and 4 h p.i. (65.4%, 85.7%, 68.5%, 96.2%, and 30.8%; cutoff threshold > 24.1%; area under curve 0.8246), respectively, and PPVs of both HMR and WR persistently showed greater than 92.7% at earlier time points and shorter time intervals. Conclusion: This study reassured that 4-h-delayed imaging is recommended for the best diagnostic performances in 123I-MIBG cardiac scintigraphy. Although it showed suboptimal diagnostic performances to differentiate PD, PDD, and DLB from non-Parkinson's diseases, it can be useful as an auxiliary measure for the differential diagnosis in usual clinical practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-023-00790-w.

[18F]MFBG PET/CT outperforming [123I]MIBG SPECT/CT in the evaluation of neuroblastoma.

PURPOSE: Iodine 123 labeled meta-iodobenzylguanidine ([123I]MIBG) scan with SPECT/CT imaging is one of the most commonly used imaging modalities in the evaluation of neuroblastoma. [18F]-meta-fluorobenzylguanidine ([18F]MFBG) is a novel positron emission tomography (PET) tracer which was reported to have a similar biodistribution to [123I]MIBG. However, the experience of using [18F]MFBG PET/CT in the evaluation of patients with neuroblastoma is limited. This preliminary investigation aims to assess the efficacy of [18F]MFBG PET/CT in the evaluation of neuroblastomas in comparison to [123I]MIBG scans with SPECT/CT. MATERIALS AND METHODS: In this prospective, single-center study, 40 participants (mean age 6.0 ± 3.7 years) with history of neuroblastoma were enrolled. All children underwent both [123I]MIBG SPECT/CT and [18F]MFBG PET/CT studies. The number of lesions and the Curie scores revealed by each imaging method were recorded. RESULTS: Six patients had negative findings on both [123I]MIBG and [18F]MFBG studies. Four of the 34 patients (11.8%) were negative on [123I]MIBG but positive on [18F]MFBG, while 30 patients were positive on both [123I]MIBG and [18F]MFBG studies. In these 34 patients, [18F]MFBG PET/CT identified 784 lesions while [123I]MIBG SPECT/CT detected 532 lesions (p < 0.001). The Curie scores obtained from [18F]MFBG PET/CT (11.32 ± 8.18, range 1-27) were statistically higher (p < 0.001) than those from [123I]MIBG SPECT/CT (7.74 ± 7.52, range 0-26). 30 of 34 patients (88.2%) with active disease on imaging had higher Curie scores based on the [18F]MFBG study than on the [123I]MIBG imaging. CONCLUSION: [18F]MFBG PET/CT shows higher lesion detection rate than [123I]MIBG SPECT/CT in the evaluation of pediatric patients with neuroblastoma. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov : NCT05069220 (Registered: 25 September 2021, retrospectively registered); Institute Review Board of Peking Union Medical College Hospital: ZS-2514.

Machine learning-based prediction of conversion coefficients for I-123 metaiodobenzylguanidine heart-to-mediastinum ratio.

PURPOSE: We developed a method of standardizing the heart-to-mediastinal ratio in 123I-labeled meta-iodobenzylguanidine (MIBG) images using a conversion coefficient derived from a dedicated phantom. This study aimed to create a machine-learning (ML) model to estimate conversion coefficients without using a phantom. METHODS: 210 Monte Carlo (MC) simulations of 123I-MIBG images to obtain conversion coefficients using collimators that differed in terms of hole diameter, septal thickness, and length. Simulated conversion coefficients and collimator parameters were prepared as training datasets, then a gradient-boosting ML was trained to estimate conversion coefficients from collimator parameters. Conversion coefficients derived by ML were compared with those that were MC simulated and experimentally derived from 613 phantom images. RESULTS: Conversion coefficients were superior when estimated by ML compared with the classical multiple linear regression model (root mean square deviations: 0.021 and 0.059, respectively). The experimental, MC simulated, and ML-estimated conversion coefficients agreed, being, respectively, 0.54, 0.55, and 0.55 for the low-; 0.74, 0.70, and 0.72 for the low-middle; and 0.88, 0.88, and 0.88 for the medium-energy collimators. CONCLUSIONS: The ML model estimated conversion coefficients without the need for phantom experiments. This means that conversion coefficients were comparable when estimated based on collimator parameters and on experiments.

123I-MIBG imaging in heart failure: impact of comorbidities on cardiac sympathetic innervation.

PURPOSE: Heart failure (HF) is a primary cause of morbidity and mortality worldwide, with significant impact on life quality and extensive healthcare costs. Assessment of myocardial sympathetic innervation function plays a central role in prognosis assessment in HF patients. The aim of this review is to summarize the most recent evidence regarding the clinical applications of iodine-123 metaiodobenzylguanidine (123I-MIBG) imaging in patients with HF and related comorbidities. METHODS: A comprehensive literature search was conducted on PubMed and Web of Science databases. Articles describing the impact of 123I-MIBG imaging on HF and related comorbidities were considered eligible for the review. RESULTS: We collected several data reporting that 123I-MIBG imaging is a safe and non-invasive tool to evaluate dysfunction of cardiac sympathetic neuronal function and to assess risk stratification in HF patients. HF is frequently associated with comorbidities that may affect cardiac adrenergic innervation. Furthermore, HF is frequently associated with comorbidities and chronic conditions, such as diabetes, obesity, kidney disease and others, that may affect cardiac adrenergic innervation. CONCLUSION: Comorbidities and chronic conditions lead to more severe impairment of sympathetic nervous system in patients with HF, with a negative impact on disease progression and outcome. Cardiac imaging with 123I-MIBG can be a useful tool to reduce morbidity and prevent adverse events in HF patients.

[18F] MFBG PET imaging: biodistribution, pharmacokinetics, and comparison with [123I] MIBG in neural crest tumour patients.

PURPOSE: Despite its limitations, [123I]MIBG scintigraphy has been the standard for human norepinephrine transporter (hNET) imaging for several decades. Recently, [18F]MFBG has emerged as a promising PET alternative. This prospective trial aimed to evaluate safety, biodistribution, tumour lesion pharmacokinetics, and lesion targeting of [18F]MFBG and perform a head-to-head comparison with [123I]MIBG in neural crest tumour patients. METHODS: Six neural crest tumour patients (4 phaeochromocytoma, 1 paraganglioma, 1 neuroblastoma) with a recent routine clinical [123I]MIBG scintigraphy (interval: - 37-75 days) were included. Adult patients (n = 5) underwent a 30-min dynamic PET, followed by 3 whole-body PET/CT scans at 60, 120, and 180 min after injection of 4 MBq/kg [18F]MFBG. One minor participant underwent a single whole-body PET/CT at 60 min after administration of 2 MBq/kg [18F]MFBG. Normal organ uptake (SUVmean) and lesion uptake (SUVmax; tumour-to-background ratio (TBR)) were measured. Regional distribution volumes (VT) were estimated using a Logan graphical analysis in up to 6 lesions per patient. A lesion-by-lesion analysis was performed to compare detection ratios (DR), i.e. fraction of detected lesions, between [18F]MFBG and [123I]MIBG. RESULTS: [18F]MFBG was safe and well tolerated. Its biodistribution was overall similar to that of [123I]MIBG, with prominent uptake in the salivary glands, liver, left ventricle wall and adrenals, and mainly urinary excretion. In the phaeochromocytoma subgroup, the median VT was 37.4 mL/cm3 (range: 18.0-144.8) with an excellent correlation between VT and SUVmean at all 3 time points (R2: 0.92-0.94). Mean lesion SUVmax and TBR at 1 h after injection were 19.3 ± 10.7 and 23.6 ± 8.4, respectively. All lesions detected with [123I]MIBG were also observed with [18F]MFBG. The mean DR with [123I]MIBG was significantly lower than with [18F]MFBG (61.0% ± 26.7% vs. 99.8% ± 0.5% at 1 h; p = 0.043). CONCLUSION: [18F]MFBG is a promising hNET imaging agent with favourable imaging characteristics and improved lesion targeting compared with [123I]MIBG scintigraphy. TRIAL REGISTRATION: Clinicaltrials.gov : NCT04258592 (Registered: 06 February 2020), EudraCT: 2019-003872-37A.