BACKGROUND: Treatment with [131I]mIBG is commonly used in pediatric metastatic neuroblastoma (NB); however, unbound [131I]I might be taken up by the thyroid, causing hypothyroidism. To prevent this occurrence, thyroid blockade with iodine salts is commonly used; despite this precaution, thyroid dysfunction still occurs. This review and meta-analysis aim to clarify the mean frequency of hypothyroidism in children with NB treated with [131I]mIBG and to investigate the possible causes.
METHODS: The literature was searched for English-language scientific manuscripts describing the incidence of TSH elevation and overt hypothyroidism in children with NB treated with [131I]mIBG. Preclinical studies, small-case series, and reviews were excluded. A proportion meta-analysis was conducted to test the influence of potentially relevant factors (type and duration of thyroid blockade, year of the study, sample size) on the incidence of TSH elevation/overt hypothyroidism.
RESULTS: Eleven studies were included. The pooled percentage of TSH elevation was 0.41 (95% CI: 0.27-0.55); the duration of the thyroid blockade (P=0.004) was inversely correlated with the incidence of TSH elevation. Moreover, a TSH increase was more common in patients treated with potassium iodide (KI) alone than in those managed with a multi-drug thyroid blockade (P<0.001). The pooled percentage of children requiring hormone replacement therapy was 0.33 (95% CI: 0.16-0.49). As in the case of TSH elevation, a longer duration of the thyroid blockade (P=0.006) and a multi-pronged approach (P<0.001) were associated with a lower incidence of overt hypothyroidism.
CONCLUSIONS: Hypothyroidism appears to occur frequently in children treated with [131I]mIBG, which should be monitored closely after the radionuclide treatment to start hormone replacement therapy as soon as needed. The duration, as well as the type of thyroid blockade, seem to influence the incidence of hypothyroidism; however, more data from prospective evaluations are needed.

BACKGROUND: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals.
METHODS: We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA).
RESULTS: Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies.
CONCLUSIONS: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.

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.

Targeted radionuclide therapy (TRT) with [131I]MIBG and [177Lu]Lu-DOTA-TATE is an alternative treatment to the classic schemes in slow progressive metastatic/inoperable paraganglioma (PGL) and pheochromocytoma (PHEO). There is no consensus on which treatment to administer and/or the best sequence in patients who are candidates for both therapies. To clarify these questions, this systematic review assesses the prognostic value of [131I]MIBG and [177Lu]Lu-DOTA-TATE (PRRT-Lu) treatments in terms of progression-free survival (PFS) both globally and considering the primary location.
This review was developed according to the PRISMA Statement with 27 final studies (608 patients). Patient characteristics, treatment procedure, and follow-up criteria were evaluated. In addition, a Bayesian linear regression model weighted according to its sample size and an alternative model, which also included an interaction between the treatment and the proportion of PHEOs, were carried out, adjusted by a Student\'s t distribution.
In linear regression models, [131I]MIBG overall PFS was, on average, 10 months lower when compared with PRRT-Lu. When considering the interaction between treatment responses and the proportion of PHEOs, PRRT-Lu showed remarkably better results in adrenal location. The PFS of PRRT-Lu was longer when the ratio of PHEOs increased, with a decrease in [131I]MIBG PFS by 1.9 months for each 10% increase in the proportion of PHEOs in the sample.
Methodology, procedure, and PFS from the different studies are quite heterogeneous. PRRT-Lu showed better results globally and specifically in PHEOs. This fact opens the window to prospective trials comparing or sequencing [131I]MIBG and PRRT-Lu.

UNASSIGNED: Pheochromocytoma is a rare tumor frequently overlooked mainly due to the wide range of its clinical presentation, which may vary from entirely untypical signs and symptoms to life-threatening complications.
UNASSIGNED: The present study aims to present a case series recently treated in our center, with emphasis placed on patients\' specific characteristics, clinical presentation and diagnostic evaluation. Relevant literature and current guidelines are being briefly reviewed to summarize screening for pheochromocytoma and appropriate diagnostic procedures.
UNASSIGNED: While the classic symptoms include headache, palpitations and sweating with permanent or paroxysmal hypertension, a wide range of clinical manifestations may be attributed to pheochromocytoma. The initial screening test is measurement of plasma or 24-hour urine metanephrine levels. Abdominal computerized tomography with intravenous contrast infusion is suggested as the imaging examination of choice, whereas magnetic resonance imaging should be preferred over CT in exceptional cases. 123I-metaiodobenzylguanidine scintigraphy is particularly useful for establishing the diagnosis of pheochromocytoma and should be further applied to detect or exclude possible metastatic lesions.
UNASSIGNED: Early diagnosis of pheochromocytoma is of great significance not only because it represents a curable form of secondary hypertension, but also because it is often related to familial syndromes, malignancy or metastatic disease. Physicians need to be familiar with relevant clinical manifestations and diagnostic steps to raise clinical suspiction of pheochromocytoma and establish a timely diagnosis.

Advances in diagnosis and treatment of cancer has improved survival but resulted in increased cardiotoxic effects. The decrease in left ventricular ejection fraction (EF), one of the pillars of diagnosis of cardiotoxicity, seems to be a late process in the evolution of the disease, so 123I-metaiodobenzylguanidine (MIBG) cardiac imaging has been proposed to detect early cardiac impairment. The aim of this systematic review was to evaluate the performance of MIBG cardiac scan in this scenario.
A systematic search was conducted in five international databases comparing MIBG parameters with EF for evaluation of cardiotoxicity. Twelve studies were included and separated in three groups. First, studies evaluating patients with established cardiotoxicity, in which EF was reduced and MIBG parameters were abnormal. Second, studies analyzing patients during or after treatment compared to controls, with MIBG parameters significantly different between groups in most studies, even when EF remained normal. Finally, studies analyzing anthracycline (ATC) dose-related changes, with alteration in MIBG parameters occurring even when EF was preserved.
Although studies had high methodological variability, cardiac sympathetic innervation imaging seems to be a promising tool for assessing early cardiotoxicity. Further studies are needed to analyze its diagnostic value in this scenario.

This systematic review aimed to evaluate the prognostic value of Iodine123 Metaiodobenzylguanidine (123I-mIBG) SPECT myocardial imaging in patients with heart failure (HF) and to assess whether semi-quantitative SPECT scores can be useful for accurate risk stratification concerning arrhythmic event (AE) and sudden cardiac death (SCD) in this cohort. A systematic literature search of studies published until November 2020 regarding the application of 123I-mIBG SPECT in HF patients was performed, in Pubmed, Scopus, Medline, Central (Cochrane Library) and Web Of Science databases, including the words \"MIBG\", \"metaiodobenzylguanidine\", \"heart\", \"spect\", and \"tomographic\". The included studies had to correlate 123I-mIBG SPECT scores with endpoints such as overall survival and prevention of AE and SCD in HF patients. According to the sixteen studies included, the analysis showed that 123I-mIBG SPECT scores, such as summed defect score (SDS), regional wash-out (rWO), and regional myocardial tracer uptake, could have a reliable prognostic value in patients with HF. An increased SDS or rWO, as well as a reduced 123I-mIBG myocardial uptake, have proven to be effective in predicting AE- and SCD-specific risk in HF patients. Despite achieved results being promising, a more reproducible standardized method for semi-quantitative analysis and further studies with larger cohort are needed for 123I-mIBG SPECT myocardial imaging to be as reliable and, thus, accepted as the conventional 123I-mIBG planar myocardial imaging.

Neuroendocrine tumour (NET) of the urinary bladder (UB) is a rare entity and comprises of well-differentiated, small cell and large cell types. Small and large cell NET like that in lung and gastrointestinal tract have an aggressive nature and are considered high-grade disease. Well-differentiated NET has been thought to be localised and having a good prognosis. We report the first case of metastatic well-differentiated NET of the UB. Our case is a 44-year-old man with well-differentiated NET of UB presented with hepatic and peritoneal metastases on initial diagnosis. He was treated with metaiodobenzylguanidine (MIBG) therapy and had a modest survival of 16 months. The primary well-differentiated NETs can present as a metastatic disease with an aggressive nature. MIBG therapy can be considered as a useful option but overall prognosis is poor. Further research is needed for better understanding and better treatment protocol.

Imperfect clinical reference standards can preclude accurately estimating the diagnostic accuracy of DAT-SPECT and MIBG myocardial scintigraphy for diagnosing DLB. To investigate the validity of unadjusted accuracy, we updated our previous meta-analysis.
Literature search was updated to March 18, 2018. We also examined published systematic review reports. Two investigators extracted data and rated study validity using the QUADAS-2 tool. We performed a Bayesian latent class model meta-analysis accounting for imperfect reference standards.
We evaluated 27 studies including 2236 patients. With the exception of two DAT-SPECT studies that involved postmortem neuropathological verification, studies were susceptible to bias from imperfect reference standards. Compared with the unadjusted accuracy estimates, the adjusted sensitivity values were similar, whereas the adjusted specificity values were generally lower for detecting α-synuclein pathology in the brain. The adjusted summary sensitivity and specificity were 0.86 (95% credible interval [CrI], 0.76-0.95) and 0.81 (CrI, 0.70-0.92), and 0.93 (CrI, 0.74-1.00) and 0.75 (CI, 0.47-0.94) for visual and semi-quantitative assessments of DAT-SPECT, respectively; 0.92 (CrI, 0.81-0.99) and 0.80 (CrI, 0.67-0.93), and 0.87 (CrI, 0.74-0.98) and 0.80 (CrI, 0.69-0.93), for delayed- and early-phase scans of MIBG scintigraphy, respectively. When diagnosing the typical clinical syndrome, the adjusted accuracy values were similar to the unadjusted estimates. The adjusted sensitivity and specificity were 0.89 (CrI, 0.75-0.98) and 0.87 (CrI, 0.72-0.97), and 0.97 (CrI, 0.78-1.0) and 0.70 (CrI, 0.43-0.92) for visual and semi-quantitative assessments of DAT-SPECT, respectively; and 0.93 (CrI, 0.81-0.98) and 0.90 (CrI, 0.73-0.97), and 0.85 (CrI, 0.66-0.96) and 0.96 (95% CI, 0.83-1.0) for delayed- and early-phase scans of MIBG scintigraphy, respectively.
In our adjusted analyses, both imaging biomarkers had high diagnostic accuracy for detecting the hallmark pathology in the brain and for diagnosing the typical clinical syndrome.

Chagas disease is caused by a parasite infection endemic of the Americas. Traditionally observed in rural areas of Latin America, current migration trends have turned Chagas disease into a global epidemic. Acute infection is rarely severe and once it resolves, some patients can develop cardiomyopathy as part of the chronic form many years later. Multiple factors related with both the host and the parasite determine the susceptibility and progression to cardiomyopathy. Current imaging techniques are able to identify cardiac autonomic denervation, perfusion abnormalities, and myocardial fibrosis at an early of stage before the development of symptoms. The prognosis of patients with Chagasic cardiomyopathy remains poor and life-threatening ventricular arrhythmias can occur at an early stage. Treatment of chronic Chagas cardiomyopathy is challenging with a great need for more studies in the field.