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Abstract: syndrome (Thyroglobulin-Elevated Negative Iodine Scintigraphy) in differentiated thyroid carcinoma is characterized by reduced expression of sodium-iodine symporter, rising serum thyroglobulin levels (Tg), and negative whole-body [131I]Iodine scans. In such patients, somatostatin receptor imaging with [68Ga]Ga-DOTATATE PET/CT (SSR PET/CT) and [18F]F-FDG PET/CT (FDG PET/CT) can identify metastases. To compare the uptake pattern of SSR PET/CT and FDG PET/CT in papillary thyroid carcinoma (PTC) patients with TENIS Syndrome under two conditions: elevated (eTSH) and suppressed (sTSH) TSH serum levels. Based on imaging findings in these patients, we intend to identify potential candidates for peptide receptor radionuclide therapy (PRRNT). Fifteen patients with PTC and TENIS Syndrome were prospectively enrolled. All patients underwent both SSR PET/CT and FDG PET/CT with sTSH and eTSH. Images were blindly evaluated for differences in SUVmax values and lesion detectability. The reference standard consisted of neck ultrasound, CT, MRI, PET/CT, biopsy, and follow-up. Three patients were selected for PRRNT due to lesion uptake similar or higher than the liver.RESULTS On a per-patient and on a per-lesion based analysis, sTSH SSR PET/CT detected a greater number of cervical and distant LNs (both p?=?0.0253 on per-patient and p?=?0.0176 and p?=?0.0391 on per-lesion, respectively) when compared to sTSH FDG PET/CT. Likewise, eTSH SSR PET/CT detected a greater number of patients with local recurrences (p?=?0.0455) and distant LN metastases (p?=?0.0143) and in a per-lesion based analysis greater number of cervical and distant LNs (p?=?0.0337 and p?=?0.0039, respectively) when compared to eTSH FDG PET/CT. No differences were found for lung and bone metastases. One of three patients submitted to 3 cycles of PRRNT presented with a visual partial response, a 20% reduction in quantitative analyses and stable disease regarding Tg and TgAb levels.CONCLUSIONS In patients with PTC and TENIS Syndrome, SSR PET/CT detected a greater number of loco-regional and distant LN metastases than FDG PET/CT with both sTSH and eTSH. One of 3 patients submitted to PRRNT presented a partial response to treatment. Our findings may impact in patient restaging, management and theranostics strategies with radiolabeled somatostatin analogs

Abstract: 6-Nitrodopamine (6-ND) is a novel endogenous catecholamine that is released from the rat isolated vas deferens, and has been characterized as a major modulator of the contractility of rat isolated epididymal vas deferens (RIEVD). Drugs such as tricyclic antidepressants, a1 and ß1ß2 adrenoceptor blockers, act as selective antagonists of the 6-ND receptor in the RIEVD. In the rat isolated atria, 6-ND has a potent positive chronotropic action and causes remarkable potentiation of the positive chronotropic effects induced by dopamine, noradrenaline, and adrenaline. Here, whether 6-ND interacts with the classical catecholamines in the rat isolated vas deferens was investigated. Incubation with 6-ND (0.1 and 1 nM; 30min) caused no contractions in the RIEVD but provoked significant leftward shifts in the concentration-response curves to noradrenaline, adrenaline, and dopamine. Pre-incubation of the RIEVD with 6-ND (1 nM), potentiated the contractions induced by electric-field stimulation (EFS), whereas pre-incubation with 1 nM of dopamine, noradrenaline or adrenaline, did not affect EFS-induced contractions. In tetrodotoxin (1 µM) pre-treated (30 min) RIEVD, pre-incubation with 6-ND (0.1 nM) did not cause leftward shifts in the concentration-dependent contractions induced by noradrenaline, adrenaline, or dopamine. Pre-incubation of the RIEVD with the a2A-adrenoceptor antagonist idazoxan (30 min, 10 nM) did not affect dopamine, noradrenaline, adrenaline, and EFS-induced contractions. However, when idazoxan (10 nM) and 6-ND (0.1 nM) were simultaneously pre-incubated (30 min), a significant potentiation of the EFS-induced contractions of the RIEVD was observed. 6-nitrodopamine causes remarkable potentiation of dopamine, noradrenaline, and adrenaline contractions on the RIEVD, due to activation of adrenergic terminals, possibly via pre-synaptic adrenoceptors

Abstract: The prognostic value of FDG PET/CT metabolic tumor burden has been established in various solid tumors, but its significance in the staging of rectal cancer remains underexplored. This study aimed to investigate the prognostic role of FDG PET/CT metabolic tumor burden in the primary staging of rectal cancer. A retrospective analysis was conducted on 82 consecutive histology-proven rectal cancer patients, including 29 females (37%), with a mean age of 60.8 years. These patients underwent staging FDG PET/CT, and various metabolic tumor burden parameters (hSUVmax, tuMTV, wbMTV, tuTLG, wbTLG) were calculated. The study assessed the correlation between metabolic tumor burden parameters and overall survival (OS), progression-free survival (PFS), as well as histopathology, clinical staging, performance status, bone-mineral indexes, hematology, and therapy management strategies. The study revealed that metabolic tumor burden, along with the presence of sarcopenia and absence of surgery, were significantly and independently associated with overall survival. Notably, a wbTLG cutoff value of 354 effectively discriminated survivors from non-survivors (p?=?0.0007) with 83% specificity. Furthermore, higher whole-body tumor burden (wbTLG: p?=?0.0090) and low body mass index (p?=?0.0231) were significantly linked to an increased risk of disease progression. This research suggests that whole-body tumor burden assessed through staging FDG PET/CT can serve as an independent imaging biomarker for prognostication in rectal cancer patients

Abstract: Pathogenic CD4+ T cells are capable of initiating neuroinflammation in experimental autoimmune encephalomyelitis (EAE). However, the precise effector mechanism of these autoaggressive CD4+ T cells is not entirely elucidated. Here, we demonstrated that pathogenic CD4+ T cells, upon autoantigen stimulation, developed a cytotoxic phenotype at the onset of EAE. The cytotoxic activity of pathogenic CD4+ T cells was sufficient to explain the initial myelin lesion. Consistently, CD4+ T cells of peripheral blood (PBMCs) and cerebrospinal fluid (CSF) from relapse-remitting multiple sclerosis (RRMS) patients present an enhancement of the cytotoxic profile in comparison with healthy control (HC). Moreover, cytotoxic CD4+ T cells (CD4-CTLs) are restrained in the PBMCs of Natalizumab-treated RRMS patients. Mechanistically, autoaggressive CD4-CTLs matched the majority of the molecular pathways of effector CD8+ T cells. Altogether, our findings point to potential new targets for monitoring MS diagnosis, treatment, and the development of novel therapeutic avenues