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espanolObjetivo Valorar la utilidad de la 18F-DOPA PET/TC cerebral en el diagnostico diferencial de lesiones cerebrales con RM no concluyente. Material y metodos Se estudiaron 12 pacientes, con un total de 16 lesiones, sin diagnostico definitivo tras RM cerebral. Se adquirio estudio 18F-DOPA PET/TC cerebral con doble adquisicion a los 20 y 90 minutos. Se realizo valoracion visual y semicuantitativa con calculo del SUVmax de las lesiones y calculo del ratio T/S (tumor/estriado contralateral) y ratio T/N (tumor/parenquima sano contralateral) para cada uno de los tiempos. Resultados Con base en la escala de valoracion visual y utilizando los ratios T/S ≥ 1 y T/N ≥ 1,3 para determinar la positividad de un estudio, los valores de sensibilidad (S), especificidad (E) y valor predictivo positivo (VPP) han sido los siguientes: valoracion visual (S 100%, E 33,3%, VPP 71,4%), ratio T/S (S 90%, E 100%, VPP 100%) y ratio T/N (S 100%, E 16,6%, VPP 66,6%). Ninguna lesion mostro un aumento del SUVmax en la adquisicion tardia. La 18F- DOPA PET/TC modifico el comportamiento terapeutico en el 75% de los pacientes. Conclusion La 18F-DOPA PET/TC es una herramienta util para diferenciar la etiologia de lesiones cerebrales con RM no concluyente. La imagen tardia (dual point) no aporta un valor anadido al diagnostico final. Los estudios con F-DOPA tienen impacto en el manejo del paciente modificando la conducta terapeutica. EnglishAim To evaluate the utility of brain 18F-DOPA PET/CT in the differential diagnosis of brain lesions with inconclusive MRI. Material and methods Twelve patients were studied, with a total of 16 lesions, without definitive diagnosis after brain MRI. A double acquisition PET/CT brain scan was acquired at 20 and 90 minutes. Visual and semiquantitative assessment was performed with SUVmax calculation of the lesions and calculation of the T/S ratio (tumor/contralateral striatum) and T/N ratio (tumor/contralateral healthy parenchyma) for each time. Results Based on the visual assessment scale and using T/S ratio ≥ 1 and T/N ratio ≥ 1.3 to determine malignancy, the values of sensitivity (S), specificity (E) and positive predictive value (PPV) were: visual assessment (S 100%, E 33.3%, VPP 71.4%), T/S ratio (S 90%, E 100%, VPP 100%) and T/N ratio (S 100%, E 16.6%, VPP 66.6%). No lesion showed an increase in SUVmax in late acquisition. 18F-DOPA PET/CT modified treatment in 75% of the patients. Conclusion 18F-DOPA PET/CT is a useful tool in the study of brain lesions with inconclusive MRI. Late imaging (dual-point) has no added value in the final diagnosis. F-DOPA has an impact on patient management modifying therapeutic behavior.

Aim To evaluate the utility of brain 18F-DOPA PET/CT in the differential diagnosis of brain lesions with inconclusive MRI. Material and methods Twelve patients were studied, with a total of 16 lesions, without definitive diagnosis after brain MRI. A double acquisition PET/CT brain scan was acquired at 20 and 90 min. Visual and semiquantitative assessment was performed with SUVmax calculation of the lesions and calculation of the T/S Ratio (tumor/contralateral striatum) and T/N Ratio (contralateral healthy tumor/parenchyma) for each time. Results Based on the visual assessment scale and using T/S ratio ≥1 and T/N ratio ≥1.3 to determine malignancy, the values of sensitivity (S), specificity (E) and positive predictive value (PPV) were: visual assessment (S 100%, E 33.3%, VPP 71.4%), T/S Ratio (S 90%, E 100%, VPP 100%) and T/N Ratio (S 100%, E 16.6%, VPP 66.6 %). No lesion showed an increase in SUVmax in late acquisition. 18F-DOPA PET/CT modified treatment in 75% of the patients. Conclusion 18F-DOPA PET/CT is a useful tool in the study of brain lesions with inconclusive MRI. Late imaging (dual-point) has no added value in the final diagnosis. FDOPA has an impact on patient management modifying therapeutic behavior.

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. 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. 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. 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. • 18 F-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.

Although antipsychotic drugs are effective for relieving the psychotic symptoms of first-episode psychosis (FEP), psychotic relapse is common during the course of the illness. While some FEPs remain remitted even without medication, antipsychotic discontinuation is regarded as the most common risk factor for the relapse. Considering the actions of antipsychotic drugs on presynaptic and postsynaptic dopamine dysregulation, this study evaluated possible mechanisms underlying relapse after antipsychotic discontinuation. Twenty five FEPs who were clinically stable and 14 matched healthy controls were enrolled. Striatal dopamine activity was assessed as Kicer value using [18F]DOPA PET before and 6 weeks after antipsychotic discontinuation. The D2/3 receptor availability was measured as BPND using [11C]raclopride PET after antipsychotic discontinuation. Healthy controls also underwent PET scans according to the corresponding schedule of the patients. Patients were monitored for psychotic relapse during 12 weeks after antipsychotic discontinuation. 40% of the patients showed psychotic relapse after antipsychotic discontinuation. The change in Kicer value over time significantly differed between relapsed, non-relapsed patients and healthy controls (Week*Group: F = 4.827, df = 2,253.193, p = 0.009). In relapsed patients, a significant correlation was found between baseline striatal Kicer values and time to relapse after antipsychotic discontinuation (R2 = 0.518, p = 0.018). BPND were not significantly different between relapsed, non-relapsed patients and healthy controls (F = 1.402, df = 2,32.000, p = 0.261). These results suggest that dysfunctional dopamine autoregulation might precipitate psychotic relapse after antipsychotic discontinuation in FEP. This finding could be used for developing a strategy for the prevention of psychotic relapse related to antipsychotic discontinuation.

Study Objective: To determine, based on data from examination of apparently healthy subjects, parameter reference values for 18F-DOPA positron emission tomography (PET) of the brain. Study Design: This was a prospective study. Materials and Methods: Apparently healthy subjects (n = 33) underwent 18F-DOPA PET of the brain using a Discovery PET/CT 600 scanner. Data were processed using standard statistical methods. The Shapiro-Wilk test was used to test data distribution for normality, and Pearson and Spearman covariance and correlation matrices were calculated. The key components were analyzed to assess combined scattering (explained variance). Study Results: For absolute parameters, the following reference levels were determined for radioactivity concentration (median [1st quartile; 3rd quartile]): 2.24 [2.02; 2.80] kBq/mL in the right putamen, 2.26 [2.02; 2.75] kBq/mL in the left putamen, 2.11 [1.78; 2.55] kBq/mL in the right caudate nucleus (CN), 2.01 [1.74; 2.49] kBq/mL in the left caudate nucleus, and 0.81 [0.71; 1.00] and 0.81 [0.74; 1.02] kBq/mL in the right and left occipital cortices (OC), respectively. For relative parameters, the following reference values were determined (mean ± standard deviation): 2.66 ± 0.52 for the right corpus striatum/OC, 2.68 ± 0.53 for the left corpus striatum/OC, 2.36 ± 0.48 for the right CN/OC, 2.34 ± 0.47 for the left CN/OC, 1.09 ± 0.21 for the right corpus striatum/CN, and 1.11 ± 0.21 for the left corpus striatum/CN. Conclusion: The paper presents reference values for radioactivity concentration in 18F-DOPA PET of the brain. This is the first report of such data. Keywords: neurodegenerative disorders, dopamine metabolism, population norm.

Purpose 18F-Fluoro- l -dihydroxyphenylalanine (18F-DOPA) PET offers high sensitivity and specificity in the imaging of non-malignant extra-adrenal paraganglioma (PGL) and pheochromocytoma (PHEO) but lower sensitivity in metastatic disease. These tumours are of neuroendocrine origin and can be detected by 68Ga-DOTA-Tyr3-octreotide (68Ga-DOTA-TOC) PET. Therefore, we compared 68Ga-DOTA-TOC and 18F-DOPA as radiolabels for PET/CT imaging for the diagnosis of metastatic extra-adrenal PGL and PHEO. Combined cross-sectional imaging was the reference standard. Methods A total of 6 men and 4 women (age range 22–72 years) with anatomical and/or histologically proven metastatic PGL and PHEO were included in this study. Of these patients, 2 male patients suffered from PHEO, while the remaining 8 patients were diagnosed as metastatic extra-adrenal PGL disease. Comparative evaluation included morphological imaging with CT and functional imaging with 68Ga-DOTA-TOC and 18F-DOPA PET. The imaging results were analyzed on a per-lesion basis. The maximum standardized uptake value (SUVmax) of each functional imaging modality in concordant tumour lesions was measured. Results Compared with anatomical imaging, the per-lesion detection rate of 68Ga-DOTA-TOC was 100% (McNemar, P Conclusion 68Ga-DOTA-TOC PET offers the highest detection rate in metastatic extra-adrenal PGL and PHEO compared to 18F-DOPA PET and even to diagnostic CT, particularly in bone lesions. Combined functional/anatomical imaging (68Ga-DOTA-TOC PET/CT) enables exact tumour extension to be detected in these rare tumour entities, especially in the case of unclear anatomical correlation.

Background: (FM). Fibromyalgia (FM) is a very prevalent and debilitating chronic pain disorder that is difficult to treat. Mindfulness-based techniques are regarded as a very promising approach for the treatment of chronic pain and in particular FM. The Mindfulness-Oriented Recovery Enhancement (MORE) intervention, a mindfulness-based group intervention, has shown beneficial effects in opioid-treated chronic pain patients, including reduced pain severity, functional interference, and opioid dosing, by restoring neurophysiological and behavioral responses to reward. First evidence for a hypodopaminergic state and impaired reward processing in FM have been reported. However, little is known about its impact on dopamine (DA) function and in particular with regard to DA responses to monetary reward in FM. The aim of the present study protocol is to evaluate if MORE is able to restore the DA function in FM patients, in particular with regard to the DA responses to reward, and to reduce pain and mood complaints in FM.Methods/design: The present study is a multi-center RCT with 3 time points: before the intervention, after completion of the intervention and 3-months after completion of the intervention. Eighty FM patients will be randomly assigned to either the MORE intervention (N=40) or to a wait-list control group (N=40). Additionally a comparison group of healthy women (N=20) will be enrolled. The MORE intervention consists of eight 2-hour long group sessions administered weekly over a period of 8 weeks. Before and after the intervention, FM participants will undergo [18F] DOPA Positron Emission Tomography (PET) and functional MR imaging while performing a monetary reward task. The primary outcome will be endogeneous DA changes measured with [18F] DOPA PET at baseline, after the intervention (after 8 weeks for control group), and at 3 months’ follow-up. Secondary outcomes will be (1) clinical pain measures and FM symptoms using standardized clinical scales 2) functional brain changes 3) measures of negative and positive affect, stress and reward experience in daily life using the Experience Sampling method (ESM) 4) biological measures of stress including cortisol and alpha-amylase.Design: If the findings of this study confirm the effectiveness of MORE in restoring DA function, reducing pain and improving mood symptoms, MORE can be judged to be a promising means to improve quality of life in FM patients. The findings of this trial may inform health care providers about the potential use of the MORE intervention as a possible non-pharmacological intervention for FM.Trial registration: ClinicalTrials.gov NCT 04451564. Registered on 3 July 2020. The trial was prospectively registered.

Rationale of the study Neuroimaging modalities such as contrast-enhanced MRI and PET provide significant insight in the evaluation of gliomas. However, their reliability in successfully differentiating the tumor recurrence with treatment-related changes is still technologically challenging. The current study aims to qualitatively investigate the potential of the hybrid PET/multiparametric MRI modality to noninvasively distinguish between these 2 outcomes of brain tumor diagnostics for optimum and early patient management. Patients and methods A cohort of 26 suspected recurrent glioma cases proved on histology and/or clinicoradiological outcome forms the part of this study. A 3-point visual analytical scale was used to qualify lesions as recurrent or posttreatment radiation effects on PET, conventional MRI, dynamic susceptibility contrast-perfusion-weighted imaging, apparent diffusion coefficient, and the MR spectroscopy according to their level of suspicion. Results Of the 26 patients, 21 patients were classified as recurrence and 5 as radiation necrosis. Advanced MRI parameters (perfusion, diffusion, and spectroscopy) integrated with 18F-DOPA PET imaging resulted in superior diagnostic performance obtained on visual assessment with an accuracy of 95%, sensitivity of 96%, and specificity approaching up to 100% over individual modalities. Conclusions The combination of multiple MR parameters evaluated together with 18F-DOPA PET offers an attractive approach to noninvasively distinguish true recurrence from radiation necrosis. However, further prospective studies with larger cohorts are warranted with additional neuropathological validations.

18F-DOPA PET-MRI was performed on a 38-year-old man referred for complementary imaging after a brain tumor was discovered, according to EANM/RANO recommendations. We performed a simultaneous PET with 3-T brain MRI, which revealed 2 high 18F-DOPA uptakes, with no multimodal MRI sign of aggressiveness. An awake surgery was performed and found a grade III anaplastic astrocytoma IDH1-R132L mutant, according to the 2016 WHO classification. This was probably the aggressive transition of a grade II diffuse astrocytoma. This case illustrates the added value of 18F-DOPA PET to multimodal MRI to distinguish low- and high-grade gliomas.

Somatostatin receptor imaging constitutes an integral part in neuroendocrine tumor visualization and should, because of its vastly superior performance, use 68Ga-DOTA-somatostatin analogue-PET/computed tomography rather than scintigraphy; it is particularly valuable for detecting metastases to lymph nodes, bone, peritoneum, and liver, which may be missed by morphologic imaging. 18FDG-PET/computed tomography is better suited for G3 and high-G2 neuroendocrine tumors. 18FDG-PET/computed tomography provides prognostic information. Alternative available PET tracers are 18F-DOPA and 11C-5-hydroxytryptophan. To take full advantage of the technique PET/computed tomography should include diagnostic intravenous contrast-enhanced computed tomography. PET/MRI is currently mainly investigational.

While dose escalation of radiotherapy (DERT) has failed to improve overall survival (OS) or progression-free survival (PFS) for glioblastoma in previous studies, a recent phase II clinical trial utilizing 18F-DOPA-PET-directed DERT demonstrated improved PFS in MGMT-unmethylated patients and OS in MGMT-methylated patients compared to historical controls. This planned secondary analysis sought to determine 1) how 18F-DOPA-PET changes RT volumes beyond standard MRI-planning, 2) which patients benefit most and least from this protocol, 3) which are mostly likely to experience clinically significant radionecrosis after DERT, and 4) patterns of failure after DERT. For 69 evaluable patients, median MRI-defined, PET-defined, and combined low-dose gross tumor volumes (GTV51) were 54 cc (range 9-248), 23 cc (0.4-179), and 62 cc (10-260), respectively. Median MRI-defined, PET-defined, and combined high-dose GTVs (GTV76) were 32 cc (range 4-136), 6 cc (0.1-138), and 34 cc (4-162), respectively. 18F-DOPA-PET resulted in a median volumetric expansion of 13% (0-243%) and 5% (0-217%) from MRI-defined low-dose and high-dose GTV’s, respectively. Central failures ( >95% of recurrence tumor volume) occurred within the 76 Gy, 60 Gy, and 51 Gy isodose lines in 32 (46%), 60 (87%), and 64 (93%) patients, respectively. Recursive partitioning analysis stratified patients by OS and PFS. Patients with 18F-DOPA-PET-defined GTV76 > 7.8cc, MRI-defined GTV76 > 42.7cc, and MGMT promotor-unmethylated tumors had the shortest OS, while patients with smaller PET and MRI-defined tumors had the longest OS (median 10.4 vs. 64.6 months, p< 0.001). Similarly, PFS was worst in patients with 18F-DOPA-PET-defined GTV76 > 2.17 cc who had biopsy only (median PFS 3.2 months, p< 0.001). Patients with 18F-DOPA-PET-defined GTV51 > 50 cc had the highest risk of grade 3+ radionecrosis (p< 0.001). In conclusion, larger 18F-DOPA-PET and MRI-defined tumor volumes were associated with worse outcomes, and 18F-DOPA-PET-directed DERT appears to reduce risk of central recurrence in high-dose volumes.

Aim The aim of this prospective observational study was to examine the benefit of a fluorine-18- L-dihydroxyphenylalanine (18F-DOPA) PET/computed tomography (CT) scan in patients with medullary thyroid carcinoma (MTC) in terms of increased calcitonin levels. Patients and methods Twenty-eight MTC patients after initial total thyreoidectomy with increasing follow-up calcitonin levels suggestive for active disease after negative conventional imaging findings (neck ultrasound or thorax, abdomen, pelvis multislice computed tomography as standard imaging) were scanned using 18F-DOPA PET/CT from November 2012 to April 2016. The mean calcitonin level was 108.5 (range: 6.7–290) pmol/l and the mean carcinoembryonic antigen level was 15.7 (range: 1.1–221.9) μg/l. The mean follow-up period was 19.7 months. Results 18F-DOPA PET/CT was positive in 16 out of 28 (57%) patients, mostly because of metabolically active neck and mediastinal lymph nodes metastases. Previously unknown bone metastases were found in six patients. A positive scan was reported in four patients (25% of positive scans) with a very low calcitonin value of less than 49.9 pmol/l. PET/CT findings led to a change of management and therapy in 16 out of 28 patients, with surgical procedure performed in eight patients, radiotherapy in five patients, and chemotherapy in two patients. Conclusion 18F-DOPA PET/CT is a clinically useful modality in MTC whenever the calcitonin level is increased. There is a clear trend toward more positive scans with the higher calcitonin values, but patients with moderately elevated calcitonin values should also be taken into consideration for molecular imaging with 18F-DOPA PET/CT as the tumor burden in these patients is probably low, enabling further therapy to be individualized and consequently more efficient

BACKGROUND Glioma often recurs and the imaging evaluation whether the tumor has returned after glioma treatment is still challenging. PET/CT is one of the most important techniques to assess the post-treatment of glioma. However, differentiating tumor recurrence (TuR) from treatment effects (TrE) remains difficult. In this study, we aim to retrospectively compare the diagnostic performance of three PET tracers 13N-NH3, 18F-DOPA, and 18F-FDG on PET/CT in differentiating between TuR and TrE in post-treatment glioma patients. METHODS Forty-three patients with MRI-suspected recurrent glioma were included. The maximum and mean standardized uptake value (SUVmax and SUVmean) of the lesion and the lesion-to-normal Gray-matter cortex uptake (L/G) ratio were recorded and the reference standard was verified by surgical histopathology or more than 6 months of follow-up with clinical/radiological. The diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. RESULTS 34 patients were confirmed as glioma TuR and 9 patients met the standard of TrE. The median time interval from primary diagnosis surgery to PET/CT was 14.83 months (range, 4.10-62.77 months). The SUVmax of 13N-NH3 and 18F-DOPA PET/CT at the lesions was significantly higher than normal brain tissue (13N-NH3 0.696±0.095 vs 0.486±0.071, 18F-DOPA 0.455±0.079 vs 0.194±0.031, both P< 0.001), while 18F-FDG was not (6.918±0.525 vs 6.356±0.510, P=0.290). TuR showed significantly higher L/G ratios than TrE both in 13N-NH3 and 18F-DOPA PET/CT (13N-NH3, 1.573±0.099 vs 1.025±0.128, P=0.008; 18F-DOPA, 2.729±0.131 vs 1.514±0.141, P< 0.001). The sensitivity, specificity and the area under the curve (AUC) by ROC analysis were 57.7, 100% and 0.803 for 13N-NH3, and 84.6, 100% and 0.938 for 18F-DOPA respectively. CONCLUSIONS PET/CT is a powerful tool to distinguish glioma TuR from TrE, and 18F-DOPA PET/CT has remarkably better differential diagnosis efficacy than 13N-NH3 and 18F-FDG.

Background Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia pathophysiology, which underlies in majority of treatment-responsive patients. Although supported by findings that prefrontal cortical lesions lead to striatal dopamine dysregulation and that recently, prefrontal structural volume is negatively correlated with striatal dopamine synthesis, the relationship between corticostriatal connectivity and striatal dopamine synthesis has not been tested in patients with schizophrenia. We therefore investigated the relationship between corticostriatal connectivity and striatal dopamine synthesis capacity in treatment-responsive patients with schizophrenia, and compared them to treatment-resistant patients and healthy control subjects. Methods Twenty-four patients with schizophrenia and twelve matched healthy control subjects underwent 18F-DOPA PET scans to measure dopamine synthesis capacity (indexed as the influx rate constant Kicer), structural and diffusion 3T MRI. Connectivity(indexed as Fractional anisotropy, FA) were assessed in 3 major corticostriatal tracts (dorsolateral prefrontal cortex-associative striatum, ventromedial prefrontal cortex-limbic striatum, and pre/primary motor cortex-sensorimotor striatum). Furthermore, these measures were tested whether they were correlated with a measure of Wisconsin Card Sorting Test (WCST). Results Treatment responsive patients showed a negative correlation between connectivity of dorsolateral prefrontal cortex-associative striatum and striatal dopamine synthesis capacity of associative striatum, but this was not evident in treatment-resistant patients. Furthermore, WCST negatively correlated with Kicer in associative striatum and positively correlated with FA in dorsolateral prefrontal cortex-associative striatum in whole subjects and treatment responsive patients but not in treatment-resistant patients. Discussion These findings demonstrate that different mechanisms underlie the pathophysiology of treatment-responsive and treatment-resistant schizophrenia and especially, connectivity of dorsolateral prefrontal cortex-associative striatum is a core part for the different pathophysiology.

A 63-year-old woman was referred to our PET/MRI platform to evaluate the possible relapse of a meningeal metastasis, complicating an invasive ductal carcinoma of the left breast. This metastasis was diagnosed on a left hemiparesis and treated by surgery and radiation therapy. One year later, the same symptoms led to another brain MRI examination that found a contrast-enhanced lesion in the operating site. We decided to perform a F-DOPA PET/MRI to document this lesion, which confirmed the diagnosis of a probable relapse and revealed a focal uptake on the bone flap.

One of the main goals in the evaluation of congenital hyperinsulinism is to distinguish medically treatable disease from disease requiring surgical management. Over the past 20 years, it has become clear that some patients with severe disease that is unresponsive to medical therapy may benefit from pancreatectomy. One of the big challenges has been distinguishing between two histopathologic forms of HI, diffuse disease, which is not curable, and focal disease, which can be cured with limited pancreatic resection. Diagnostic evaluation with the 18-F-L-3,4-dihydroxyphenylalanine [18F]-DOPA PET scan has been shown to have moderate-good sensitivity for diagnosis of a focal lesion but almost 100% accuracy in localizing a detected lesion. The finding of a focal lesion can change surgical approach, decrease surgical morbidity, and lead to a cure of this devastating disease.

I tumori neuroendocrini (NET) stanno assumendo un ruolo sempre piu importante nell’ambito della patologia oncologica. In considerazione della loro estrema eterogeneita l’approccio diagnostico-terapeutico risulta complesso e necessita di una gestione multidisciplinare. Lo sviluppo della PET/TC con la possibilita di utilizzare diversi traccianti ha permesso un notevole ampliamento delle conoscenze sul comportamento dei NET e ha aperto nuovi orizzonti per la diagnosi e la terapia di tali neoplasie.

PET investigation of human brain for the purposes of the effective diagnostics of some neurodegenerative diseases requires the definition of the normal indices. Here we present the figures to be used as the reference values of the necessary indices to be used in medical investigations.

We report the finding of increased F-DOPA uptake within parenchyma surrounding a developmental venous anomaly, found incidentally in a 64-year-old woman undergoing PET scan to assess for Parkinson's disease. Not identified on previous T1/T2 MRI, susceptibility-weighted imaging MRI performed post-PET scan demonstrated the presence of developmental venous anomaly within the left cerebellar hemisphere. Focal uptake of F-DOPA may suggest the presence of a brain tumor and prompt invasive diagnostic investigations. Nuclear medicine physicians should be aware of this finding when interpreting F-DOPA PET and consider appropriate imaging to identify venous anomalies prior to more invasive investigations for possible brain tumors.

Purpose & Methods: Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using68Ga-DOTA-conjugated peptides, as well as18F-DOPA imaging for various neuroendocrine neoplasms. Results & Conclusion: The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with68Ga-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts.

Medullary thyroid cancer (MTC) is considered as a rare thyroid cancer. Surgical approaches such as, total thyroidectomy and bilateral lymph node dissection, represent the first-line treatment. Persistent or increasing serum levels of tumor markers, such as CEA and calcitonin, imply residual or recurrent disease. An early and precise detection of recurrence is very important for guiding appropriate treatment. Recent developments in positron emission tomography (PET) imaging with different radiopharmaceuticals targeting specific hallmark of MTC, such as 18F-DOPA and 18F-FDG, have offered increased sensitivity for identifying recurrences. Moreover, the ability of conventional scintigraphic imaging to guide the surgical approach can be useful for the treatment of MTC recurrent patients. In the present work, we reported two cases of patients with recurrent MTC sending to surgical treatment guided by “nuclear medicine approaches”.

High-grade gliomas (HGGs) are the most common malignant primary tumors of the central nervous system. PET probes of amino acid transport such as O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET), 3,4-dihydroxy-6-(18)F-fluoro-l-phenylalanine ((18)F-DOPA), and (11)C-methionine ((11)C-MET) detect primary and recurrent tumors with a high accuracy. (18)F-FET is predominantly used in Europe, whereas amino acid transport imaging is infrequently done in the United States. The aim of this study was to determine whether (18)F-FET and (18)F-DOPA PET/CT provide comparable information in HGG.Thirty (18)F-FET and (18)F-DOPA PET/CT scans were obtained before surgery or biopsy in 27 patients with high clinical suspicion for primary or recurrent HGG (5 primary, 22 recurrent tumors). (18)F-FET and (18)F-DOPA PET/CT images were compared visually and semiquantitatively (maximum standardized uptake value [SUV(max)], mean SUV [SUV(mean)]). Background (SUV(max) and SUV(mean)) and tumor-to-background ratios (TBRs) were calculated for both PET probes. The degree of (18)F-DOPA uptake in the basal ganglia (SUV(mean)) was also assessed.Visual analysis revealed no difference in tumor uptake pattern between the 2 PET probes. The SUV(mean) and SUV(max) for (18)F-FET were higher than those of (18)F-DOPA (4.0 ± 2.0 and 4.9 ± 2.3 vs. 3.5 ± 1.6 and 4.3 ± 2.0, respectively; all P0.001). TBRs for SUV(mean) but not for SUV(max) were significantly higher for (18)F-FET than (18)F-DOPA (TBR SUV(mean): 3.8 ± 1.7 vs. 3.4 ± 1.2, P = 0.004; TBR SUV(max): 3.3 ± 1.6 and 3.0 ± 1.1, respectively; P = 0.086). (18)F-DOPA uptake by the basal ganglia was present (SUV(mean), 2.6 ± 0.7) but did not affect tumor visualization.Whereas visual analysis revealed no significant differences in uptake pattern for (18)F-FET and (18)F-DOPA in patients with primary or recurrent HGG, both SUVs and TBRs for SUV(mean) were significantly higher for (18)F-FET. However, regarding tumor delineation, both tracers performed equally well and seem equally feasible for imaging of primary and recurrent HGG. These findings suggest that both PET probes can be used based on availability in multicenter trials.

18F-DOPA is a radiopharmaceutical with interesting clinical applications and promising performances in the evaluation of the integrity of dopaminergic pathways, brain tumors, NETs (especially MTCs, paragangliomas, and pheochromocytomas), and congenital hyperinsulinism. 18F-DOPA traces a very specific metabolic pathway and has a very precise biodistribution pattern. As for any radiopharmaceutical, the knowledge of the normal distribution of 18F-DOPA, its physiologic variants, and its possible pitfalls is essential for the correct interpretation of PET scans. Moreover, it is important to be aware of the potential false-positive and false-negative episodes that can occur in the various clinical settings.

Purpose The aim of this study was to investigate the relationship between 123I-metaiodobenzylguanidine (MIBG) scan semi-quantification and a new 18F-DOPA positron emission tomography (PET)/CT score in patients with suspected or documented neuroblastoma (NB) relapse and to assess the association between these two parameters and progression-free survival (PFS)/overall survival (OS).

A 40-year-old female patient with suspected multifocal extra-adrenal paraganglioma, on the basis of biochemical, genetic, and conventional imaging data, underwent 18F-FDG, 18F-DOPA and 68Ga DOTANOC PET/CT. FDOPA- and FDG-PET/CT detected a multifocal mediastinal and cervical paraganglioma. 68Ga-DOTANOC PET/CT detected 2 additional lesions compared to the other PET/CT methods. In our case, somatostatin receptor PET/CT with 68Ga-DOTANOC correctly assessed the extent of the disease in a patient with multifocal paraganglioma.

Pancreatic neuroendocrine neoplasm (pNEN) prevalence is increasing as a consequence of both the improvement of diagnostic procedures and therapeutic options. Although pNEN is characterised by an overall better prognosis as compared to other forms of solid tumours, the patient outcome can vary greatly.

A 53-year-old-woman is being followed up for a sporadic medullary thyroid carcinoma that was initially treated surgically. Nine years later, a progressive increase in calcitonin levels along with headaches was observed. An orbital metastasis from medullary thyroid carcinoma was diagnosed by performing an F-DOPA PET/CT. The orbital lesion was treated by an external beam radiation. Four months later, an MRI revealed a global morphological stability and a reduction in calcitonin levels.

We report the finding of increased F-3,4-dihydroxyphenylalanine uptake of the brain parenchyma adjacent to developmental venous anomalies, incidentally discovered in 3 pediatric patients with diffusely infiltrating gliomas. One patient presented 3 developmental venous anomalies located distant from the tumor, whereas in the remaining 2 patients, the vascular anomalies were inside the tumoral area mimicking a focal area of increased tumor metabolism. In the setting of brain tumor imaging, focal increased F-3,4-dihydroxyphenylalanine uptake should be carefully interpreted in light of MRI findings, and nuclear medicine physicians should be aware of any incidental minor vascular abnormality for proper interpretation of PET data.

To verify the potential role and feasibility of carbidopa premedication in pediatric patients undergoing ¹⁸F-DOPA (Fluorine-18 fluorodihydroxyphenylalanine) PET scanning. MATERIALS AND METHODS: For this limited study, 5 patients (M:F=3:2; mean age 4.8 years) with a positive history for neuroblastoma who had been referred to our institution for instrumental monitoring during clinical follow-up were enrolled. In all cases, two consecutive ¹⁸F-DOPA PET scans, the first without carbidopa and the second with carbidopa premedication, were scheduled: patients received 4 MBq/kg of radiotracer and a dose of 2 mg/kg of carbidopa. Dedicated VOIs were drawn on the basal ganglia, pancreas, liver, and renal cortex. These regions were semiquantitatively analyzed at both the first and at the second ¹⁸F-DOPA scan, and mean SUV(max) values were compared using the t-test. RESULTS: On a visual basis, a clear reduction in the abdominal accumulation of (18)F-DOPA was observed in all cases after carbidopa premedication. This reduction related both to the biliary structures and the excretory system, and was accompanied by a generalized increase in soft tissue uptake. The semiquantitative analysis documented an absolute increase in SUV(max) after carbidopa premedication in the basal ganglia (3.4±1.3 vs. 2.1±0.8) and liver parenchyma (2.2±0.5 vs. 1.5±0.5), whereas SUV(max) decreased in the renal cortex (1.7±0.8 vs. 3.7±1.0) and the pancreas (2.3±0.6 vs. 3.5±0.5). The changes in SUV(max) were statistically significant for the pancreas and liver parenchyma (p=0.022 and 0.045, respectively), but not for the basal ganglia and renal cortex (p=0.143 and 0.15, respectively). CONCLUSIONS: Carbidopa premedication in the pediatric population appears feasible and seems to influence ¹⁸F-DOPA distribution in the liver and pancreas in a manner similar to that reported in adults. Larger series are however needed to properly define the clinical role of carbidopa premedication in children.

The objective of this study was to give an overview of the potential clinical utility of [18F]-L-dihydroxyphenylalanine (18F-DOPA) PET and PET/CT for imaging of brain tumors. Review articles and reference lists were used to supplement the search findings. 18F-DOPA has been investigated as a PET tracer for primary brain tumors, metastases of somatic cancer, and evaluation of relapse of pathology in patients with brain tumor after surgery and/or radiotherapy on the basis of enhanced cell proliferation. Available studies have provided encouraging preliminary results for diagnosis of brain tumors and relapse after surgery/radiotherapy. In the brain, excellent discrimination between tumor and normal tissue can be achieved because of the low physiological uptake of 18F-DOPA and the high ratio between tumor and normal hemispheric tissue. Information on evaluation of brain metastases is limited but encouraging. PET and PET/CT with 18F-DOPA are useful in diagnosing primary brain tumors and should be recommended in the diagnosis of relapse of disease after surgical treatment and/or radiotherapy. Semiquantitative analysis could improve diagnosis while correlative imaging with MRI is essential. Limits are due to low knowledge of potential pitfalls.

Erratum to : Guideline for PET/CT imaging of neuroendocrine neoplasms with 68Ga-DOTA-conjugated somatostatin receptor targeting peptides and 18F-DOPA.

Purpose The aim of the study was to estimate normal ranges and test-retest measures for various parameters characterising dopamine metabolism from a prolonged 18F-dopa positron emission tomography (PET) measurement using a reference tissue model and compare their value for the detection of early Parkinson’s disease (PD).

BACKGROUND: Multiple studies have demonstrated that amino acid PET tracers identify aggressive disease beyond what is contrast enhancing on T1-weighted conventional MR (T1CE). In this study, we explored discrepancies between 18F-DOPA PET and conventional MR for defining target volumes in newly diagnosed glioblastoma (GBM) radiotherapy patients. METHODS: In an ongoing NCI-funded trial (NCT:R01CA178200), 18F-DOPA PET was acquired prior to chemoradiation for newly diagnosed GBM patients and incorporated prospectively into the target volumes, modifying low and high dose target volumes, and guiding dose escalation to the most aggressive disease. Based on the results of our pilot biopsy-validation study, two 18F-DOPA PET volumes were defined, one with a T/N threshold >2.0 (PET_high) depicting the most aggressive disease and another with a T/N threshold default of ≥1.5 (PET_low) with modifications if needed by a Nuclear Medicine physician. Both PET volumes were compared with the T1CE+cavity MR volumes for 30 MGMT unmethylated newly diagnosed GBM patients. RESULTS: The PET_low volume extended beyond T2-FLAIR signal abnormality for all patients, and extended beyond standard CTV expansion in 60% of patients. Sixty-seven per cent of patients had at least 20% of the PET_high uptake outside the T1CE volume, and would not have been covered by standard CTV expansion in 8% of patients. The average (range) Dice Similarity Coefficient comparing T1CE with PET_high was 0.3(0.0–0.7). The average (range) Haursdorff maximum distance (cm) between PET uptake and T1CE was found to be 2.4(0.9–7.1). CONCLUSIONS: 18F-DOPA-PET identified regions of biologically active disease outside the T1CE in 67% of patients with significant discordance in volumes. Evaluation of the impact prospective 18F-DOPA PET guidance for dose escalated radiation therapy is under investigation in the ongoing trial.

Congenital hyperinsulinism is a leading cause of severe hypoglycaemia in the newborn period. There are two (diffuse and focal) histological subtypes of congenital hyperinsulinism. The diffuse form affects the entire pancreas and if medically unresponsive will require a near total (95%-98%) pancreatectomy. The focal form affects only a small region of the pancreas (with the rest of the pancreas being normal in endocrine and exocrine function) and only requires a limited pancreatectomy. This limited section of the focal lesion has the potential for curing the patient. Thus the pre-operative differentiation of these two subgroups is extremely important. Recent advances in Fluorine-18-L-dihydroxyphenylalanine positron emission tomography ((18)F-DOPA PET/CT) have radically changed the clinical approach to patient with congenital hyperinsulinism. In most patients this novel imaging technique is able to offer precise pre-operative localisation of the focal lesion, thus guiding the extent of surgical resection.

The following affiliation should be added to the authors Agostino Chiaravalloti and Orazio Schillaci.

Background Recent meta-analysis revealed that elevated presynaptic striatal dopaminergic function is a robust feature of psychosis like schizophrenia. Considering increased dopaminergic capacity in psychotic disorders, it is not surprising that antipsychotic drugs, which primarily block dopaminergic neurotransmission, are mostly effective in the treatment of psychosis. However, it remains obscure what would happen to presynaptic dopaminergic function with antipsychotic treatment. This is an important issue addressing whether the current antipsychotic drugs are correcting the primary dopaminergic abnormality or not. In addition, the issue can give a clue regarding the mechanism of relapse in psychotic disorders. Methods We measured presynaptic dopamine capacity using [18F]DOPA PET before and after the antipsychotic discontinuation in first episode psychosis. The binding potentials of [11C]raclopride were also measured after the discontinuation. Healthy controls had [18F]DOPA and [11C]raclopride scans at the corresponding date. First episode psychosis patients were carefully monitored in the aspects of symptomatic aggravations. Results The presynaptic dopamine capacity and the density of dopamine receptors showed significant group effect and the interaction between group and time (p

Despite highly specific radiopharmaceuticals like 111 In-Octreotide or 123 I-MIBG, detection of small neuroendocrine tumours (NET) can be hampered due to the limited resolution of planar scintigraphy and SPECT. 18 F-FDG, the workhorse in oncological high resolution PET diagnostic, is mainly positive in undifferentiated NETs. For 18 F-DOPA, a limited number of studies are published, demonstrating favourable results in tumour detection of NETs. The role of 18 F-DOPA in comparison to 68 Ga-labeled somatostatin-receptor ligands will have to be defined in future studies.

In recent years, considerable progress has been made in the biochemical, morphological and molecular genetic differentiation of congenital hyperinsulinism (CHI). Fluorine-18 L-3,4-dihydroxyphenylalanine positron emission tomography (18F-DOPA-PET) has been introduced for differentiation between focal and diffuse CHI. The ability to take up L-DOPA and convert it into dopamine is correlated with the activity of the aromatic amino acid decarboxylase and increased in the hyperfunctional affected pancreatic area in comparison to normally functioning pancreas. The high sensitivity of this method allows the surgeon to perform a curative limited resection of a focus without the risk of long-term diabetes. The exact preoperative planning by 18F-DOPA-PET/CT computer tomography allows laparoscopic operation in selected cases with the focus in the tail and limits necessity to open the pancreatic duct in cases with focus in the head. Patients with persistent CHI should be managed within a strong network of diagnostic, treatment, and research institutions.

Summary:Preoperative localization of parathyroid adenomas (PA) can shorten operation time and improve curative rate; it becomes especially important in minimally invasive surgical techniques. Aim of this study was to investigate whether positron emission tomography (PET) with 3-,4-dihydroxy- 6-18F-fluorophenylalanine (18F-DOPA), which showed very promising results in other neuroendocrine tumours, also helps to localize PA. Patients, methods: Eight patients with proven primary hyperparathyroidism were studied preoperatively with PET. Seven also underwent scintigraphy with 99mTc-MIBI and ultrasonography of the neck. All patients were operated and the histological finding was used as a gold standard. Results: All eight patients had a histologically proven PA. None of the PA showed any detectable uptake of 18F-DOPA. However, ultrasonography detected 5/7 PA, scintigraphy detected 3/7 PA. Conclusion: These results suggest that PET with 18F-DOPA is not useful in the detection of PA in patients with primary hyperparathyroidism.