Head-to-head comparison between [68Ga]Ga-DOTA-NOC and [18F]DOPA PET/CT in a diverse cohort of patients with pheochromocytomas and paragangliomas.

PURPOSE: To compare the detection ability of 68Ga-labelled DOTA-l-Nal3-octreotide ([68Ga]Ga-DOTA-NOC) and 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]DOPA) in patients with phaeochromocytomas and paragangliomas (PPGLs) of different origins and gene mutations, such as germline succinate dehydrogenase complex genes (SDHx). METHODS: Eighty-five patients with histopathologically confirmed PPGLs who underwent both [68Ga]Ga-DOTA-NOC and [18F]DOPA PET/CT from March 2017 to June 2023 were enrolled in this retrospective study. For comparative analyses, PPGLs were classified as phaeochromocytoma (PCC), sympathetic paraganglioma (sPGL), and head/neck paraganglioma (HNPGL). Detection rates were analyzed on per-patient and per-lesion bases and compared using the Chi-square/Fischer's exact test. RESULTS: Among 85 patients with PPGLs (48 males; 43 years ± 17 [SD]), the patient-based detection rates of [68Ga]Ga-DOTA-NOC and [18F]DOPA PET/CT were 87.1% (74/85) and 89.4% (76/85), respectively (p = 0.634), and the lesion-based detection rates were 80.8% (479/593) and 71.2% (422/593), respectively (p < 0.001). Only one patient with a recurrent PCC presented double-negative imaging, while 66 patients exhibited double-positive imaging. The remaining patients were either [68Ga]Ga-DOTA-NOC-negative/[18F]DOPA-positive (n = 10) or [68Ga]Ga-DOTA-NOC-positive/[18F]DOPA-negative (n = 8). In subgroup analyses, [68Ga]Ga-DOTA-NOC PET/CT detected significantly more metastases of sPGL (91.1%, 236/259) and SDHx-related PPGL (89.6%, 86/96) than [18F]DOPA PET/CT (48.6%[126/259] and 50.0%[48/96], respectively; both p < 0.001). However, [18F]DOPA showed significantly higher detection rates of PCC in both primary/recurrent and metastatic lesions (94.3%[50/53] vs. 62.3%[33/53] and 87.9%[174/198] vs. 69.2%[137/198], respectively; both p < 0.001). Regarding metastases in different organs, [68Ga]Ga-DOTA-NOC PET/CT detected more lesions than [18F]DOPA PET/CT in bone (96.2%[176/183] vs. 66.1%[121/183]; p < 0.001) and lymph nodes (82.0%[73/89] vs. 53.9%[48/89]; p < 0.001) but less lesions in peritoneum (20%[4/20] vs. 100%[20/20]; p < 0.001). CONCLUSION: [68Ga]Ga-DOTA-NOC and [18F]DOPA are complementary in diagnosing PPGL under the appropriate clinical setting. [68Ga]Ga-DOTA-NOC should be considered as the ideal first-line tracer for detecting metastases of sPGL and SDHx-related tumours, whereas [18F]DOPA may be the optimal tracer for evaluating non-SDHx-related PCC, especially in detecting primary lesions and monitoring recurrence.

Molecular imaging and related therapeutic options for medullary thyroid carcinoma: state of the art and future opportunities.

Due to its rarity and non-specific clinical presentation, accurate diagnosis, and optimal therapeutic strategy of medullary thyroid carcinoma (MTC) remain challenging. Molecular imaging provides valuable tools for early disease detection, monitoring treatment response, and guiding personalized therapies. By enabling the visualization of molecular and cellular processes, these techniques contribute to a deeper understanding of disease mechanisms and the development of more effective clinical interventions. Different nuclear imaging techniques have been studied for assessing MTC, and among them, PET/CT utilizing multiple radiotracers has emerged as the most effective imaging method in clinical practice. This review aims to provide a comprehensive summary of the current use of advanced molecular imaging modalities, with a particular focus on PET/CT, for the management of patients with MTC. It aims to guide physicians towards a rationale for the use of molecular imaging also including theranostic approaches and novel therapeutical opportunities. Overall, we emphasize the evolving role of nuclear medicine in MTC. The integration of diagnostics and therapeutics by in vivo molecular imaging represents a major opportunity to personalize treatment for individual patients, with targeted radionuclide therapy being one representative example.

[Congenital hyperinsulinism : contributions of chemistry, therapeutic response, genetics and imaging]. / Hyperinsulinisme congénital : apports de la biologie, de la réponse thérapeutique, de la génétique et de l'imagerie.

Congenital hyperinsulinism is the most common cause of recurrent hypoglycemia in newborns and children. Early diagnosis and rapid management are essential to avoid hypoglycaemic brain injury and later neurological complications. Management of those patients involves biological evaluation, molecular genetics, imaging techniques and surgical advances. We report the case of a newborn with recurrent hypoglycemia due to congenital hyperinsulinism (CHI) caused by a new variant in the ABCC8 gene. Fluorine 18-L-3,4 Dihydroxyphenylalanine Positron Emission Tomography (18F-DOPA PET/CT scan) reported a focal lesion at the isthmus of the pancreas which has been removed by laparoscopic surgery with a complete recovery for the patient.

L'hyperinsulinisme congénital est la cause la plus fréquente d'hypoglycémies récidivantes chez le nouveau-né et l'enfant. Un diagnostic et une prise en charge précoces sont primordiaux pour éviter les conséquences potentielles sur le développement neurologique. Ces derniers reposent sur la conjonction d'éléments biologiques, génétiques et d'imagerie. Nous rapportons le cas d'un nouveau-né présentant des hypoglycémies récidivantes. La mise au point mettra en évidence un hyperinsulinisme congénital (CHI) lié à un variant non encore décrit au sein du gène ABCC8. L'imagerie par Fluorine 18-L-3,4 Dihydroxyphenylalanine Positron Emission Tomography/Computed Tomography-scanner (18F-DOPA PET/CT scan) a mis en évidence une forme focale de l'hyperinsulinisme justifiant une prise en charge chirurgicale amenant à une guérison complète et à l'arrêt de tout traitement médicamenteux.

Onset pattern of nigrostriatal denervation in early Parkinson's disease.

The striatal dopaminergic deficit in Parkinson's disease exhibits a typical pattern, extending from the caudal and dorsal putamen at onset to its more rostral region as the disease progresses. Clinically, upper-limb onset of cardinal motor features is the rule. Thus, according to current understanding of striatal somatotopy (i.e. the lower limb is dorsal to the upper limb) the assumed pattern of early dorsal striatal dopaminergic denervation in Parkinson's disease does not fit with an upper-limb onset. We have examined the topography of putaminal denervation in a cohort of 23 recently diagnosed de novo Parkinson's disease patients and 19 age-/gender-matched healthy subjects assessed clinically and by 18F-DOPA PET; 15 patients were re-assessed after 2 years. There was a net upper-limb predominance of motor features at onset. Caudal denervation of the putamen was confirmed in both the more- and less-affected hemispheres and corresponding hemibodies. Spatial covariance analysis of the most affected hemisphere revealed a pattern of 18F-DOPA uptake rate deficit that suggested focal dopamine loss starting in the posterolateral and intermediate putamen. Functional MRI group-activation maps during a self-paced motor task were used to represent the somatotopy of the putamen and were then used to characterize the decline in 18F-DOPA uptake rate in the upper- and lower-limb territories. This showed a predominant decrement in both hemispheres, which correlated significantly with severity of bradykinesia. A more detailed spatial analysis revealed a dorsoventral linear gradient of 18F-DOPA uptake rate in Parkinson's disease patients, with the highest putamen denervation in the caudal intermediate subregion (dorsoventral plane) compared to healthy subjects. The latter area coincides with the functional representation of the upper limb. Clinical motor assessment at 2-year follow-up showed modest worsening of parkinsonism in the primarily affected side and more noticeable increases in the upper limb in the less-affected side. Concomitantly, 18F-DOPA uptake rate in the less-affected putamen mimicked that recognized on the most-affected side. Our findings suggest that early dopaminergic denervation in Parkinson's disease follows a somatotopically related pattern, starting with the upper-limb representation in the putamen and progressing over a 2-year period in the less-affected hemisphere. These changes correlate well with the clinical presentation and evolution of motor features. Recognition of a precise somatotopic onset of nigrostriatal denervation may help to better understand the onset and progression of dopaminergic neurodegeneration in Parkinson's disease and eventually monitor the impact of putative therapies.

Beyond Visual Assessment of Basal Ganglia Uptake: Can Automated Method and Pineal Body Uptake Assessment Improve Identification of Nigrostriatal Dysfunction on 18F-DOPA PET/CT?

The interpretation of 18F-DOPA PET/CT performed for assessing nigrostriatal dysfunction (NSD) is usually based on visual assessment of the uptake in the basal ganglia (VA-BG). In the present study, we evaluate the diagnostic performance of an automated method that assesses BG uptake (AM-BG) and of methods that assess pineal body uptake, and examine whether these methods can enhance the diagnostic performance of VA-BG alone. We retrospectively included 112 scans performed in patients with clinically suspected NSD who also had a subsequent final clinical diagnosis provided by a movement disorder specialist (69 NSD and 43 non-NSD patients). All scans were categorized as positive or negative based on (1) VA-BG, (2) AM-BG, and (3) qualitative and semiquantitative assessment of pineal body uptake. VA-BG, AM-BG, assessment of pineal body 18F-DOPA uptake by VA (uptake > background), by SUVmax (≥0.72), and by pineal to occipital ratio (POR ≥ 1.57) could all significantly differentiate NSD from non-NSD patients (Pv < 0.01 for all five methods). Of these methods, VA-BG provided the highest sensitivity (88.4%) and accuracy (90.2%). Combining VA-BG with AM-BG did not improve diagnostic accuracy. An interpretation algorithm that combines VA-BG with pineal body uptake assessment by POR calculation increased sensitivity to 98.5%, at the expense of decreased specificity. In conclusion, an automated method that assesses 18F-DOPA uptake in the BG and assessment of pineal body 18F-DOPA uptake can significantly separate NSD from non-NSD patients, with apparent inferior diagnostic performance when applied alone compared with VA-BG. When VA-BG categorizes a scan as negative or equivocal, assessment of the 18F-DOPA uptake in the pineal body has the potential to minimize the rate of false negative reports. Further research is essential to validate this approach and to study the pathophysiologic relationship between 18F-DOPA uptake in the pineal body and nigrostriatal dysfunction.

Prognostic value of texture analysis of the primary tumour in high-risk neuroblastoma: An 18 F-DOPA PET study.

PURPOSE: To evaluate the prognostic value of texture analysis of the primary tumour with 18 fluorine-dihydroxyphenylalanine positron emission tomography/X-ray computed tomography (18 F-DOPA PET/CT) in patients affected by high-risk neuroblastoma (HR-NBL). METHODS: We retrospectively analysed 18 patients with HR-NBL, which had been prospectively enrolled in the course of a previous trial investigating the diagnostic role of 18 F-DOPA PET/CT at the time of the first onset. Texture analysis of the primary tumour was carried out on the PET images using LifeX. Conventional indices, histogram parameters, grey level co-occurrence (GLCM), run-length (GLRLM), neighbouring difference (NGLDM) and zone-length (GLZLM) matrices parameter were extracted; their values were compared with the overall metastatic load, expressed by means of whole-body metabolic burden (WBMB) score and the progression-free/overall survival (PFS and OS). RESULTS: There was a direct correlation between WBMB and radiomics parameter describing uptake intensity (SUVmean : p = .004) and voxel heterogeneity (entropy: p = .026; GLCM_Contrast: p = .001). Conversely, texture indices of homogeneity showed an inverse correlation with WBMB (energy: p = .026; GLCM_Homogeneity: p = .006). On the multivariate model, WBMB (p < .01) and the first standardised uptake value (SUV) quartile (p < .001) predicted PFS; OS was predicted by WBMB and the N-myc proto-oncogene protein (MYCN) amplification (p < .05) for both. CONCLUSIONS: Textural parameters describing heterogeneity and metabolic intensity of the primary HR-NBL are closely associated with its overall metastatic burden. In turn, the whole-body tumour load appears to be one of the most relevant predictors of progression-free and overall survival.

Head-to-head comparison between 18 F-DOPA PET/CT and 68 Ga-DOTA peptides PET/CT in detecting intestinal neuroendocrine tumours: A systematic review and meta-analysis.

PURPOSE: The imaging of intestinal neuroendocrine tumours (NETs) relies on functional positron emission tomography (PET) tracers; these tumours can be studied by means of both 68 Ga-DOTA peptides and 18 F-fluorodihydroxyphenyl- l-alanine (18 F-DOPA) PET/computed tomography (CT). As yet, it is unclear which of these two modalities offers the better sensitivity. We therefore conducted a meta-analysis to assess the available data. METHODS: PubMed, CENTRAL, Scopus and Web of Science were searched for studies comparing the sensitivity of 68 Ga-DOTA peptides and 18 F-DOPA PET/CT; papers up to February 2021 were considered. In each study, we considered sensitivity in terms of patient-based analysis (PBA), region-based analysis (RBA) and lesion-based analysis (LBA), and pooled the results yielded by each tracer. Multidisciplinary follow-up served as the standard of truth. RESULTS: Of the 636 records identified, 6 articles published between 2008 and 2021 were finally selected, and 112 intestinal NETs patients were included. The pooled sensitivity of 18 F-DOPA PET/CT was 83%, 89% and 95% on PBA, RBA and LBA, respectively. 68 Ga-DOTA peptides PET/CT showed sensitivity of 88%, 92% and 82% on PBA, RBA and LBA, respectively. No significant differences were found between the two tracers on PBA and RBA. By contrast, a clear trend towards significance in favour of 18 F-DOPA PET/CT was identified on LBA. The presence of a significant difference in favour of 18 F-DOPA PET/CT was confirmed in a subgroup analysis conducted only on the most recent and largest studies. In all three analyses, mild-to-high heterogeneity was found; however, no publication bias was observed. CONCLUSION: Both 18 F-DOPA PET/CT and 68 Ga-DOTA-peptides PET/CT are reliable diagnostic procedures in patients with intestinal NETs. However, in terms of lesion detection, a non-negligible difference in favour of 18 F-DOPA PET/CT was observed. Thus, the use of 18 F-DOPA PET/CT could be considered as a first-line molecular procedure in intestinal NETs.

The role of the deep convolutional neural network as an aid to interpreting brain [18F]DOPA PET/CT in the diagnosis of Parkinson's disease.

OBJECTIVES: To test the performance of a 3D convolutional neural network (CNN) in analysing brain [18F]DOPA PET/CT in order to identify patients with nigro-striatal neurodegeneration. We evaluated the robustness of the 3D CNN by testing it against a manual regional analysis of the striata by using a striatal-to-occipital ratio (SOR). METHODS: We analyzed patients who had undergone [18F]DOPA PET/CT from 2016 to 2018. Two examiners interpreted PET/CT images as positive or negative. Only patients with at least 2 years of follow-up and an ascertained neurological diagnosis were included. A 3D CNN was developed to evaluate [18F]DOPA PET/CT and refine the diagnosis of movement disorder. This system required training and testing, which were carried out on 2/3 and 1/3 of patients, respectively. A regional analysis was also conducted by drawing region of interest on T1-weighted 3D MRI scans, on which the [18F]DOPA PET images were first co-registered. RESULTS: Ninety-eight patients were enrolled: 43 presented nigro-striatal degeneration and 55 negative cases used as controls. After training on 69 patients, the diagnostic performance of the 3D CNN was then calculated in 29 patients. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy were 100%, 89%, 100%, 85% and 93%, respectively. When we compared the 3D CNN results with the SOR analysis, we found that the two patients falsely classified as positive by the 3D CNN procedure showed SOR values ≤ 5th percentile of the negative cases' distribution. CONCLUSIONS: 3D CNNs are able to interpret [18F]DOPA PET/CT properly, revealing patients affected by Parkinson's disease. KEY POINTS: • [18F]DOPA PET/CT is a sensitive diagnostic tool to identify patients with nigro-striatal neurodegeneration. • A semiquantitative evaluation of the images allows a more confident interpretation of the PET findings. • 3D convolutional neural network allows an accurate interpretation of 18F-DOPA PET/CT images, revealing patients affected by Parkinson's disease.

Prognostic impact of bone metastases detected by 18F-DOPA PET in patients with metastatic midgut neuroendocrine tumors.

OBJECTIVES: Bone metastases (BM) may influence negatively the prognosis of midgut neuroendocrine tumors (NET). The diagnostic sensitivity of 18F-DOPA PET for midgut NET and associated metastases is high. This study aimed to assess the prognostic impact of BM detected by 18F-DOPA PET in metastatic midgut NET. METHODS: All patients with a metastatic midgut NET, who underwent a 18F-DOPA PET between June 2011 and June 2018, were included. BM were defined following imaging criteria and were classified as poly-BM or oligo-BM, according to their number (< 5 or ≥ 5, respectively). The variables associated with the presence of BM were evaluated by logistic regression. The factors associated with overall survival were explored by Cox regression models. RESULTS: Among 155 patients included, 46 had BM (29.7%). A carcinoid syndrome (OR 2.96, p = 0.009) and ≥ 3 extra-skeletal metastatic organs (OR 4.99, p = 0.002) were independently associated with the presence of BM. BM were mainly osteoblastic (78%), rarely symptomatic (8.9%), and had a short-term therapeutic impact for 3 patients (6.5%). The presence of BM (HR 2.67, p = 0.034), older age (HR 1.07, p = 0.016), and higher Ki67 (HR 1.09, p = 0.025) were independent prognostic factors. Unlike poly-BM (HR 1.92, p = 0.007), oligo-BM was not a poor prognosis factor (HR 0.77, p = 0.699) compared to the group without BM. CONCLUSION: 18F-DOPA PET frequently detects BM in patients with metastatic midgut NET. BM have a negative prognostic impact, especially poly-BM. Conversely, oligo-BM do not influence the prognosis and may not impact therapeutic decisions. KEY POINTS: • 18F-DOPA PET detected bone metastases in 46 (29.7%) of 155 patients with metastatic midgut neuroendocrine tumors. • Bone metastases have a negative prognostic impact in metastatic midgut neuroendocrine tumors. • Bone oligo-metastases (< 5) do not influence the prognosis and may not impact therapeutic decisions.

Aberrant striatal dopamine links topographically with cortico-thalamic dysconnectivity in schizophrenia.

Aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei are among the most consistent large-scale brain imaging findings in schizophrenia. A pathophysiological link between these two alterations is suggested by theoretical models based on striatal dopamine's topographic modulation of cortico-thalamic connectivity within cortico-basal-ganglia-thalamic circuits. We hypothesized that aberrant striatal dopamine links topographically with aberrant cortico-thalamic iFC, i.e. aberrant associative striatum dopamine is associated with aberrant iFC between the salience network and thalamus, and aberrant sensorimotor striatum dopamine with aberrant iFC between the auditory-sensorimotor network and thalamus. Nineteen patients with schizophrenia during remission of psychotic symptoms and 19 age- and sex-comparable control subjects underwent simultaneous fluorodihydroxyphenyl-l-alanine PET (18F-DOPA-PET) and resting state functional MRI (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure striatal dopamine synthesis capacity; correlation coefficients between rs-fMRI time series of cortical networks and thalamic regions of interest were used to measure iFC. In the salience network-centred system, patients had reduced associative striatum dopamine synthesis capacity, which correlated positively with decreased salience network-mediodorsal-thalamus iFC. This correlation was present in both patients and healthy controls. In the auditory-sensorimotor network-centred system, patients had reduced sensorimotor striatum dopamine synthesis capacity, which correlated positively with increased auditory-sensorimotor network-ventrolateral-thalamus iFC. This correlation was present in patients only. Results demonstrate that reduced striatal dopamine synthesis capacity links topographically with cortico-thalamic intrinsic dysconnectivity in schizophrenia. Data suggest that aberrant striatal dopamine and cortico-thalamic dysconnectivity are pathophysiologically related within dopamine-modulated cortico-basal ganglia-thalamic circuits in schizophrenia.

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management.

Hyperinsulinemic hypoglycemia (HH) is characterized by unregulated insulin release, leading to persistently low blood glucose concentrations with lack of alternative fuels, which increases the risk of neurological damage in these patients. It is the most common cause of persistent and recurrent hypoglycemia in the neonatal period. HH may be primary, Congenital HH (CHH), when it is associated with variants in a number of genes implicated in pancreatic development and function. Alterations in fifteen genes have been recognized to date, being some of the most recently identified mutations in genes HK1, PGM1, PMM2, CACNA1D, FOXA2 and EIF2S3. Alternatively, HH can be secondary when associated with syndromes, intra-uterine growth restriction, maternal diabetes, birth asphyxia, following gastrointestinal surgery, amongst other causes. CHH can be histologically characterized into three groups: diffuse, focal or atypical. Diffuse and focal forms can be determined by scanning using fluorine-18 dihydroxyphenylalanine-positron emission tomography. Newer and improved isotopes are currently in development to provide increased diagnostic accuracy in identifying lesions and performing successful surgical resection with the ultimate aim of curing the condition. Rapid diagnostics and innovative methods of management, including a wider range of treatment options, have resulted in a reduction in co-morbidities associated with HH with improved quality of life and long-term outcomes. Potential future developments in the management of this condition as well as pathways to transition of the care of these highly vulnerable children into adulthood will also be discussed.

Reduced striatal dopamine synthesis capacity in patients with schizophrenia during remission of positive symptoms.

While there is consistent evidence for increased presynaptic dopamine synthesis capacity in the striatum of patients with schizophrenia during psychosis, it is unclear whether this also holds for patients during psychotic remission. This study investigates whether striatal dopamine synthesis capacity is altered in patients with schizophrenia during symptomatic remission of positive symptoms, and whether potential alterations relate to symptoms other than positive, such as cognitive difficulties. Twenty-three patients with schizophrenia in symptomatic remission of positive symptoms according to Andreasen, and 24 healthy controls underwent 18F-DOPA-PET and behavioural-cognitive assessment. Imaging data were analysed with voxel-wise Patlak modelling with cerebellum as reference region, resulting in the influx constant kicer reflecting dopamine synthesis capacity. For the whole striatum and its subdivisions (i.e. limbic, associative, and sensorimotor), averaged regional kicer values were calculated, compared across groups, and correlated with behavioural-cognitive scores, including a mediation analysis. Patients had negative symptoms (Positive and Negative Syndrome Scale-negative 14.13 ± 5.91) and cognitive difficulties, i.e. they performed worse than controls in Trail-Making-Test-B (TMT-B; P = 0.01). Furthermore, kicer was reduced in patients for whole striatum (P = 0.004) and associative (P = 0.002) and sensorimotor subdivisions (P = 0.007). In patients, whole striatum kicer was negatively correlated with TMT-B (rho = -0.42, P = 0.04; i.e. the lower striatal kicer, the worse the cognitive performance). Mediation analysis showed that striatal kicer mediated the group difference in TMT-B. Results demonstrate that patients with schizophrenia in symptomatic remission of positive symptoms have decreased striatal dopamine synthesis capacity, which mediates the disorder's impact on cognitive difficulties. Data suggest that striatal dopamine dysfunction contributes to cognitive difficulties in schizophrenia.

Congenital hyperinsulinism: management and outcome, a single tertiary centre experience.

Hyperinsulinemic hypoglycaemia (HH) is the most frequent cause of persistent hypoglycaemia in neonates and infants. The most severe forms of HH are inherited and referred to as congenital hyperinsulinism (CHI). Diazoxide is the mainstay of treatment, with surgery being an option in appropriate cases. To describe the management and outcome of patients with CHI within our service. Children referred to or attending HH clinic between 2009 and 2017 were identified. Clinical course, genetics and interventions were documented. A total of 39 children were identified, and seven patients with secondary and syndromic HH were excluded. Most were born with an appropriate weight for gestational age (62.5%). Diazoxide was started in all patients; however, 7 did not respond and required octreotide/continuous feeding, with 6/7 requiring surgery. Genetic mutations were detected in 12/32 (37.5%). Hyperinsulinism resolved in conservatively treated patients within 12 months in 11/32 (34.3%) compared to 14/32 (43.7%) requiring more than 12 months of medication. A total of 7 patients underwent pancreatectomy.Conclusion: Although LGA and SGA are risk factors, most babies in our cohort are born AGA. A genetic mutation does not exclude medical remission; long-term conservative treatment of CHI is feasible as surgery does not guarantee complete remission.What is Known:•Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disorder that is the most common cause of permanent hypoglycaemia in infants and children.•Identification of genetic mutations and the use of 18F-DOPA PET scan when feasible lead to better outcomes.What is New:•The study describes clinical criteria, management and outcome of large number of patients with CHI in single tertiary centre.•Conservative treatment is feasible without the need for surgery, with HH resolving in over 30% within 12 months, irrespective of genetic mutation.

18F-DOPA PET/CT in brain tumors: impact on multidisciplinary brain tumor board decisions.

PURPOSE: This study aimed to assess the therapeutic impact and diagnostic accuracy of 18F-DOPA PET/CT in patients with glioblastoma or brain metastases. METHODS: Patients with histologically proven glioblastoma or brain metastases were prospectively included in this monocentric clinical trial (IMOTEP). Patients were included either due to a clinical suspicion of relapse or to assess residual tumor infiltration after treatment. Multimodality brain MRI and 18F-DOPA PET were performed. Patients' data were discussed during a Multidisciplinary Neuro-oncology Tumor Board (MNTB) meeting. The discussion was first based on clinical and MRI data, and an initial diagnosis and treatment plan were proposed. Secondly, a new discussion was conducted based on the overall imaging results, including 18F-DOPA PET. A second diagnosis and therapeutic plan were proposed. A retrospective and definitive diagnosis was obtained after a 3-month follow-up and considered as the reference standard. RESULTS: One hundred six cases were prospectively investigated by the MNTB. All patients with brain metastases (N = 41) had a clinical suspicion of recurrence. The addition of 18F-DOPA PET data changed the diagnosis and treatment plan in 39.0% and 17.1% of patients' cases, respectively. Concerning patients with a suspicion of recurrent glioblastoma (N = 12), the implementation of 18F-DOPA PET changed the diagnosis and treatment plan in 33.3% of cases. In patients evaluated to assess residual glioblastoma infiltration after treatment (N = 53), 18F-DOPA PET data had a lower impact with only 5.7% (3/53) of diagnostic changes and 3.8% (2/53) of therapeutic plan changes. The definitive reference diagnosis was available in 98/106 patients. For patients with tumor recurrence suspicion, the adjunction of 18F-DOPA PET increased the Younden's index from 0.44 to 0.53 in brain metastases and from 0.2 to 1.0 in glioblastoma, reflecting an increase in diagnostic accuracy. CONCLUSION: 18F-DOPA PET has a significant impact on the management of patients with a suspicion of brain tumor recurrence, either glioblastoma or brain metastases, but a low impact when used to evaluate the residual glioblastoma infiltration after a first-line radio-chemotherapy or second-line bevacizumab.

The role of exposure to pesticides in the etiology of Parkinson's disease: a 18F-DOPA positron emission tomography study.

Susceptibility to Parkinson's disease (PD) is believed to involve an interaction between genetic and environmental factors. The role of pesticides as a risk factor of PD and neurodegeneration remains controversial. An asymmetric decrease in ligand uptake on 18F-DOPA positron emission tomography (PET), especially in the dorsal putamen, is a sensitive marker of PD. The aim of this study was to examine the pattern of ligand uptake on 18F-DOPA PET in patients with PD exposed or not exposed to pesticides. The main sample included 26 Israeli patients with PD, 13 who were exposed to pesticides and 13 who were not, matched for age and disease duration. All underwent 18F-DOPA PET imaging, and an asymmetry index of ligand uptake between the ipsilateral and contralateral caudate, putamen, and whole striatum was calculated. No significant between-group differences were found in demographic variables, clinical asymmetry index (P = 0.15), or asymmetry index of ligand uptake in the putamen (P = 0.84), caudate (P = 0.78) and striatum (P = 0.45). Comparison of the 18F-DOPA results of the Israeli cohort with those of 17 non-pesticide-exposed patients with PD from Austria yielded no significant differences, further validating our findings. Our observations suggest that although exposure to pesticides might be a risk factor for PD, it does not have an effect on the asymmetry pattern in the nigrostriatal system over non-exposure. We assume that once the disease process is initiated in pesticide-exposed patients, the pathogenic mechanism does not differ from that of idiopathic PD.

Hyperinsulinaemic hypoglycaemia-an overview of a complex clinical condition.

Hyperinsulinaemic hypoglycaemia (HH) is a major cause of hypoglycaemia in the neonatal period, infancy and childhood. It is caused by unsuppressed insulin secretion in the setting of hypoglycaemia and carries a high risk of significant neurological sequelae, such as cognitive impairment. Genetic mutations have been implicated in the pathogenesis of the condition. Other causes include intra-uterine growth retardation, perinatal asphyxia, maternal diabetes mellitus and syndromes, such as Beckwith-Wiedemann. Based on the aetiology, the clinical presentation can range from absence of symptoms to the typical adrenergic symptoms and coma and even death. The diagnosis is based on biochemical findings and the gold-standard imaging technique is 18F-DOPA PET/CT scanning. Treatment options involve medications, such as diazoxide, nifedipine, glucagon and octreotide, as well as surgery. Novel treatment, such as long-acting octreotide, lanreotide and sirolimus, may be used as an alternative to pancreatectomy. Potential future medical treatments include exendin, a GLP-1 receptor antagonist, and glucagon infusion via a pump.Conclusion: Advances in the fields of genetic testing, imaging techniques and medical treatment are beginning to provide novel insights into earlier detection, less invasive treatment approaches and fewer complications associated with the complex entity of hyperinsulinaemic hypoglycaemia. What is Known: • HH is caused by dysregulated insulin release from the ß cell due to genetic mutations and carries a risk for complications, such as neurocognitive impairment. 18F-DOPA PET/CT scanning is presented as the gold-standard imaging technique currently in children with hyperinsulinaemic hypoglycaemia. • Clinical presentation is heterogeneous and treatment options include medical therapy and pancreatectomy. What is New: • 18F-DOPA PET/CT is indicated in suspected focal CHI due to paternal transmitted mutations in ABCC8 or KCNJ11. • Novel treatment options have been introduced, such as long-acting octreotide, lanreotide, sirolimus and selective nonpeptide somatostatin receptor subtype 5 (SSTR5) agonists. Future medical treatments include exendin, a GLP-1 antagonist, and glucagon infusion via a pump. However, all these options are off-label at present.

Extrastriatal monoaminergic dysfunction and enhanced microglial activation in idiopathic rapid eye movement sleep behaviour disorder.

BACKGROUND: The majority of patients diagnosed with idiopathic rapid eye movement sleep behaviour disorder (iRBD) progress over time to a Lewy-type α-synucleinopathy such as Parkinson's disease or dementia with Lewy bodies. This in vivo molecular imaging study aimed to investigate if extrastriatal monoaminergic systems are affected in iRBD patients and if this coincides with neuroinflammation. METHODS: We studied twenty-one polysomnography-confirmed iRBD patients with 18F-DOPA and 11C-PK11195 positron emission tomography (PET) to investigate extrastriatal monoaminergic function and microglial activation. Twenty-nine healthy controls (n = 9 18F-DOPA and n = 20 11C-PK11195) were also investigated. Analyses were performed within predefined regions of interest and at voxel-level with Statistical Parametric Mapping. RESULTS: Regions of interest analysis detected monoaminergic dysfunction in iRBD thalamus with a 15% mean reduction of 18F-DOPA Ki values compared to controls (mean difference = -0.00026, 95% confidence interval [-0.00050 to -0.00002], p-value = 0.03). No associated thalamic changes in 11C-PK11195 binding were observed. Other regions sampled showed no 18F-DOPA or 11C-PK11195 PET differences between groups. Voxel-level interrogation of 11C-PK11195 binding identified areas with significantly increased binding within the occipital lobe of iRBD patients. CONCLUSION: Thalamic monoaminergic dysfunction in iRBD patients may reflect terminal dysfunction of projecting neurons from the locus coeruleus and dorsal raphe nucleus, two structures that regulate REM sleep and are known to be involved in the early phase of PD. The observation of significantly raised microglial activation in the occipital lobe of these patients might suggest early local Lewy-type α-synuclein pathology and possibly an increased risk for later cognitive dysfunction.

Spontaneous eye blink rate and dopamine synthesis capacity: preliminary evidence for an absence of positive correlation.

Dopamine is central to a number of cognitive functions and brain disorders. Given the cost of neurochemical imaging in humans, behavioural proxy measures of dopamine have gained in popularity in the past decade, such as spontaneous eye blink rate (sEBR). Increased sEBR is commonly associated with increased dopamine function based on pharmacological evidence and patient studies. Yet, this hypothesis has not been validated using in vivo measures of dopamine function in humans. To fill this gap, we measured sEBR and striatal dopamine synthesis capacity using [18 F]DOPA PET in 20 participants (nine healthy individuals and 11 pathological gamblers). Our results, based on frequentist and Bayesian statistics, as well as region-of-interest and voxel-wise analyses, argue against a positive relationship between sEBR and striatal dopamine synthesis capacity. They show that, if anything, the evidence is in favour of a negative relationship. These results, which complement findings from a recent study that failed to observe a relationship between sEBR and dopamine D2 receptor availability, suggest that caution and nuance are warranted when interpreting sEBR in terms of a proxy measure of striatal dopamine.

[18F]DOPA PET/ceCT in diagnosis and staging of primary medullary thyroid carcinoma prior to surgery.

PURPOSE: Medullary thyroid carcinoma (MTC) is characterized by a high rate of metastasis. In this study we evaluated the ability of [18F]DOPA PET/ceCT to stage MTC in patients with suspicious thyroid nodules and pathologically elevated serum calcitonin (Ctn) levels prior to total thyroidectomy and lymph node (LN) dissection. METHODS: A group of 32 patients with sonographically suspicious thyroid nodules and pathologically elevated basal Ctn (bCtn) and stimulated Ctn (sCtn) levels underwent DOPA PET/ceCT prior to surgery. Postoperative histology served as the standard of reference for ultrasonography and DOPA PET/ceCT region-based LN staging. Univariate and multivariate regression analyses as well as receiver operating characteristic analysis were used to evaluate the correlations between preoperative and histological parameters and postoperative tumour persistence or relapse. RESULTS: Primary MTC was histologically verified in all patients. Of the 32 patients, 28 showed increased DOPA decarboxylase activity in the primary tumour (sensitivity 88%, mean SUVmax 10.5). Undetected tumours were exclusively staged pT1a. The sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53% and 73%, in contrast to 20% and 39%, respectively, for neck ultrasonography. Preoperative bCtn and carcinoembryonic antigen levels as well as cN1b status and the number of involved neck regions on DOPA PET/ceCT were predictive of postoperative tumour persistence/relapse in the univariate regression analysis (P < 0.05). Only DOPA PET/ceCT cN1b status remained significant in the multivariate analysis (P = 0.016, relative risk 4.02). CONCLUSION: This study revealed that DOPA PET/ceCT has high sensitivity in the detection of primary MTC and superior sensitivity in the detection of LN metastases compared to ultrasonography. DOPA PET/ceCT identification of N1b status predicts postoperative tumour persistence. Thus, implementation of a DOPA-guided LN dissection might improve surgical success.

Guidelines on nuclear medicine imaging in neuroblastoma.

Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on 123I-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with 18F-FDG, 18F-DOPA and 68Ga-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.