Intraindividual comparison of 18 F-FDOPA and 68 Ga-DOTATOC PET/CT detection rate for metastatic assessment in patients with ileal neuroendocrine tumours.

INTRODUCTION: In patients with ileal neuroendocrine tumours (ileal NETs), head-to-head evaluation of diagnostic performances of 68 Ga-DOTA-peptides and 18 F-fluorodihydroxyphenylalanine (18 F-FDOPA) positron emission tomography/computed tomography (PET/CT) has been performed in only few small patients' cohorts. The aim of this retrospective study was to compare 68 Ga-DOTATOC and 18 F-FDOPA PET/CT for metastatic disease assessment in a homogeneous large series of patients with well-differentiated ileal NETs. METHODS: All patients with ileal NETs who underwent both 18 F-FDOPA and 68 Ga-DOTATOC PET/CT within a 3-month period and no therapeutic change between the two studies were retrospectively included. The detection rates of both modalities were calculated using per-patient, per-region and per-lesion analyses. RESULTS: Forty one patients with ileal NETs were evaluated. 18 F-FDOPA and 68 Ga-DOTATOC showed similar detection rates according to per-patient (97% for both) and per-region analyses (94% for 18 F-FDOPA vs 88% for 68 Ga-DOTATOC, P = .35). For a total of 605 positive lesions, 458 (76%) were detected by both modalities, 122 (20%) exclusively by 18 F-FDOPA PET/CT, and 25 (4%) by 68 Ga-DOTATOC PET/CT only. In a per-lesion analysis, 18 F-FDOPA PET/CT performed better than 68 Ga-DOTATOC PET/CT (overall detection rates of 96% vs 80%; P < .001). 18 F-FDOPA PET/CT detected significantly more metastases than 68 Ga-DOTATOC PET/CT in the liver, peritoneum, abdominal and supra-diaphragmatic lymph nodes. CONCLUSION: 18 F-FDOPA PET/CT seems not inferior than 68 Ga-DOTATOC PET/CT for the delineation of metastatic spread of ileal NETs. Therefore, according to local expertise and technical availability, 18 F-FDOPA should be considered as a valid clinical diagnostic option for exhaustive metastatic assessment in patients with ileal NETs. Obviously, 68 Ga-DOTATOC PET/CT remains mandatory for PRRT assessment. Further comparative studies are needed to determine the optimal approach in various clinical scenarios such as preoperative staging and primary tumour detection.

Metabolomic characterization of human hippocampus from drug-resistant epilepsy with mesial temporal seizure.

OBJECTIVE: Within a complex systems biology perspective, we wished to assess whether hippocampi with established neuropathological features have distinct metabolome. Apparently normal hippocampi with no signs of sclerosis (noHS), were compared to hippocampal sclerosis (HS) type 1 (HS1) and/or type 2 (HS2). Hippocampus metabolome from patients with epilepsy-associated neuroepithelial tumors (EANTs), namely, gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs), was also compared to noHS epileptiform tissue. METHODS: All patients underwent standardized temporal lobectomy. We applied 1 H high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy to 48 resected human hippocampi. NMR spectra allowed quantification of 21 metabolites. Data were analyzed using multivariate analysis based on mutual information. RESULTS: Clear distinct metabolomic profiles were observed between all studied groups. Sixteen and 18 expected metabolite levels out of 21 were significantly different for HS1 and HS2, respectively, when compared to noHS. Distinct concentration variations for glutamine, glutamate, and N-acetylaspartate (NAA) were observed between HS1 and HS2. Hippocampi from GG and DNT patients showed 7 and 11 significant differences in metabolite concentrations when compared to the same group, respectively. GG and DNT had a clear distinct metabolomic profile, notably regarding choline compounds, glutamine, glutamate, aspartate, and taurine. Lactate and acetate underwent similar variations in both groups. SIGNIFICANCE: HRMAS NMR metabolomic analysis was able to disentangle metabolic profiles between HS, noHS, and epileptic hippocampi associated with EANT. HRMAS NMR metabolomic analysis may contribute to a better identification of abnormal biochemical processes and neuropathogenic combinations underlying mesial temporal lobe epilepsy.

Effect of Carbidopa on 18F-FDOPA Uptake in Insulinoma: From Cell Culture to Small-Animal PET Imaging.

Patient premedication with carbidopa seems to improve the accuracy of 6-18F-fluoro-3,4-dihydroxy-l-phenylalanine (18F-FDOPA) PET for insulinoma diagnosis. However, the risk of PET false-negative results in the presence of carbidopa is a concern. Consequently, we aimed to evaluate the effect of carbidopa on 18F-FDOPA uptake in insulinoma ß-cells and an insulinoma xenograft model in mice. METHODS: 18F-FDOPA in vitro accumulation was assessed in the murine ß-cell line RIN-m5F. In vivo small-animal PET experiments were performed on tumor-bearing nude mice after subcutaneous injection of RIN-m5F cells. Experiments were conducted with and without carbidopa pretreatment. RESULTS: Incubation of RIN-m5F cells with 80 µM carbidopa did not significantly affect the cellular accumulation of 18F-FDOPA. Tumor xenografts were clearly detectable by small-animal PET in all cases. Insulinoma xenografts in carbidopa-treated mice showed significantly higher 18F-FDOPA uptake than those in nontreated mice. Regardless of carbidopa premedication, the xenografts were characterized by an early increase in 18F-FDOPA uptake and then a progressive reduction over time. CONCLUSION: Carbidopa did not influence in vitro 18F-FDOPA accumulation in RIN-m5F cells but improved insulinoma imaging in vivo. Our findings increase current knowledge about the 18F-FDOPA uptake profile of RIN-m5F cells and a related xenograft model. To our knowledge, the present work represents the first preclinical research specifically focused on insulinomas, with potential translational implications.

Carbidopa-assisted 18F-fluorodihydroxyphenylalanine PET/CT for the localization and staging of non-functioning neuroendocrine pancreatic tumors.

OBJECTIVE: CD premedication was found to increase the value of 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT imaging in the detection of adult insulinoma. The aim of this study was to evaluate the performance of CD-assisted 18F-FDOPA PET/CT in the diagnosis and staging of non-functioning pNETs. METHODS: Twenty consecutive patients with low-grade pNETs who underwent CD-assisted 18F-FDOPA PET/CT imaging and 111In-somatostatin receptor scintigraphy (SRS) were evaluated. Histology was considered as the gold standard. In case where no surgical resection was performed, the diagnosis of pNET was made by the confrontation of the different available imaging modalities. RESULTS: CD-assisted 18F-FDOPA PET/CT was positive in 18/20 cases (90 %), whereas SRS was positive in 13/19 cases (68 %). When considered the 19 patients underwent both nuclear medicine examinations, 18F-FDOPA PET/CT was significantly more sensitive then SRS for primary tumor detection (p = 0.049). False-negative results of both 18F-FDOPA PET/CT and SRS were observed in 2 cystic pNETs. SRS failed to detect one additional cystic tumor and 3 pNETs of 10, 12 and 17 mm, respectively. 18F-FDOPA PET/CT correctly identified all patients with lymphatic, visceral and bone metastases. SRS failed to detect lymphatic spread and was falsely negative in one patient with splenic metastasis. CONCLUSIONS: Contrary to widely held assumptions, our study further expands the application of CD-assisted 18F-FDOPA PET/CT for non-functioning pNETs when 68Ga-radiolabeled somatostatin analogs are not available.

18F-fluorodihydroxyphenylalanine PET/CT in patients with neuroendocrine tumors of unknown origin: relation to tumor origin and differentiation.

UNLABELLED: This work was performed to evaluate the performance of (18)F-fluorodihydroxyphenylalanine ((18)F-FDOPA) PET/CT in detecting primary neuroendocrine tumors (NETs) occult on morphologic and functional imaging, in relation to tumor origin and differentiation. METHODS: A retrospective study of NET patients who were investigated with (18)F-FDOPA PET/CT imaging in 2 academic endocrine tumor centers was conducted. Only patients with negative conventional and somatostatin receptor scintigraphy (SRS) results were studied. RESULTS: Twenty-seven patients were evaluated with (18)F-FDOPA PET/CT, 23 at their initial staging and 4 during their follow-up. The primary occult NET was localized by (18)F-FDOPA PET/CT in 12 patients (overall sensitivity, 44%; 52% in patients evaluated at initial diagnosis), leading to tumor resection in all cases. The primary tumors were distributed and graded as follows: 1 duodenum G2 lesion, 7 ileum G2 lesions, 2 terminal ileum G1 lesions, 1 pancreas G2 lesion, and 1 gallbladder G3 lesion. Patients with positive (18)F-FDOPA PET/CT results had higher values of serum chromogranin A (100% vs. 20%, P = 0.0003), serotonin, or urinary 5-hydroxyindolacetic acid (83% vs. 20%, P = 0.003). Two false-negative results were related to poorly differentiated duodenal and prostatic NETs (G3). (18)F-FDOPA PET/CT showed more metastatic anatomic regions than SRS in 17 patients. CONCLUSION: (18)F-FDOPA PET appears to be a sensitive functional imaging tool for the detection of primary NETs occult on SRS, especially tumors with a well-differentiated pattern and serotonin secretion.

18F-fluorocholine uptake in a case of adrenal incidentaloma: possible diagnostic pitfall or potential tool for adrenocortical tumors characterization?

The understanding of radiotracer's physiological biodistribution as well as the potential source of false-positive results is crucial for an accurate diagnostic interpretation of (18)F-fluorocholine PET/CT examination in patients with prostate cancer. We illustrate the results of whole-body (18)F-fluorocholine PET/CT in a 79-year-old man with biochemical suspicion of prostate adenocarcinoma relapse. PET/CT study showed a focally increased (18)F-fluorocholine uptake, characterizing an incidentally found adrenocortical adenoma. Finally, we draw oncologists' attention to the possible false-positive results of (18)F-fluorocholine PET related to benign and unsuspected adrenocortical lesions in patients with a history of prostate malignancy.

A 5-month period of epilepsy impairs spatial memory, decreases anxiety, but spares object recognition in the lithium-pilocarpine model in adult rats.

PURPOSE: In temporal lobe epilepsy (TLE), interictal behavioral disorders affect patients' quality of life. Therefore we studied long-term behavioral impairments in the lithium-pilocarpine (li-pilo) model of TLE. METHODS: Eleven li-pilo adult rats exhibiting spontaneous recurrent seizures (SRSs) during 5 months were compared with 11 li-saline rats. Spatial working memory was tested in a radial arm maze (RAM), anxiety in an elevated plus-maze (EPM), and nonspatial working memory in an object-recognition paradigm. Neuronal loss was assessed on thionine brain sections after behavioral testing. RESULTS: In the RAM, the time to complete each session and the number of errors per session decreased over a 5-day period in li-saline rats but remained constant and significantly higher in li-pilo rats. In the EPM, the number of entries in and time spent on open arms were significantly higher in li-pilo than li-saline rats. In the object-recognition task, the two groups exhibited a comparable novelty preference for the new object. Neuronal loss reached 47-90% in hilus, CA1, amygdala, and piriform and entorhinal cortex. CONCLUSIONS: In li-pilo rats having experienced SRS for 5 months, performance in the object-recognition task is spared, which suggests that object discrimination remains relatively intact despite extensive damage. Neuronal loss in regions mediating memory and anxiety, such as hippocampus, entorhinal cortex, and amygdala, may relate to impaired spatial orientation and decreased anxiety.