Neurotensin (8-13) and Neuromedin N Neuropeptides Radiolabelling with Copper-64 Produced on Solid or Liquid Targets.

On the verge of a theranostic approach to personalised medicine, copper-64 is one of the emerging radioisotopes in nuclear medicine due to its exploitable nuclear and biochemical characteristics. The increased demand for copper-64 for preclinical and clinical studies has prompted the development of production routes. This research aims to compare the (p,n) reaction on nickel-64 solid versus liquid targets and evaluate the effectiveness of [64Cu]CuCl2 solutions prepared by the two routes. As new treatments for neurotensin receptor-overexpressing tumours have developed, copper-64 was used to radiolabel Neurotensin (8-13) and Neuromedin N. High-quality [64Cu]CuCl2 solutions were prepared using ACSI TR-19 and IBA Cyclone Kiube cyclotrons. The radiochemical purity after post-irradiation processing reached 99% (LT) and 99.99% (ST), respectively. The irradiation of a solid target with 11.8 MeV protons and 150 µAh led to 704 ± 84 MBq/µA (17.6 ± 2.1 GBq/batch at EOB). At the end of the purification process (1 h, 90.90% activity yield), the solution for peptide radiolabelling had a radioactive concentration of 1340.4 ± 70.1 MBq/mL (n.d.c.). The irradiation of a liquid target with 16.9 MeV protons and 230 µAh resulted in 3.7 ± 0.2 GBq/batch at EOB, which corresponds to an experimental production yield of 6.89 GBq.cm3/(g.µA)sat. Benefiting from a shorter purification process (40 min), the activity yielded 90.87%, while the radioactive concentration of the radiolabelling solution was lower (492 MBq/mL, n.d.c.). The [64Cu]CuCl2 solutions were successfully used for the radiolabelling of DOTA-NT(8-13) and DOTA-NN neuropeptides, resulting in a high RCP (>99%) and high molar activity (27.2 and 26.4 GBq/µmol for LT route compared to 45 and 52 GBq/µmol for ST route, respectively). The strong interaction between the [64Cu]Cu-DOTA-NT(8-13) and the colon cancerous cell lines HT29 and HCT116 proved that the specificity for NTR had not been altered, as shown by the uptake and retention data.

Sequence of Rare Diagnoses in a Young Patient: Altitude Barotrauma Hemopneumothorax and Desquamative Interstitial Pneumonia.

We present the case of a 35-year-old patient without pathological history who developed hemopneumothorax due to altitude barotrauma during a commercial airline flight. The computed tomography (CT) of the chest identified the presence of right hydropneumothorax and emphysema "blebs" and bubbles. After the therapeutic insertion of a drain tube, the patient returned to the country by land transport. Three weeks later, he was diagnosed with right-sided pleurisy based on a CT scan with contrast material. A surgical intervention was then performed, and three biopsy samples were taken; the histopathological result highlighted suggestive elements for the diagnosis of desquamative interstitial pneumonia (DIP).

Preparation and Preliminary Evaluation of Neurotensin Radiolabelled with 68Ga and 177Lu as Potential Theranostic Agent for Colon Cancer.

The neurotensin is a tridecapeptide involved in the proliferation of colon cancer, the overexpression of neurotensin receptors occurring at an early stage development of many tumours. Targeting neurotensin receptors by using the same biological active molecule is an effective approach for both imaging quantification and treatment. The present work aimed to demonstrate the ability of radiolabelled neurotensin to specifically target colon cancer cells, and substantiate its usefulness in targeted imaging and radiotherapy, depending on the emission of the coupled radioisotope. Syntheses of 68Ga-DOTA-NT and 177Lu-DOTA-NT were developed to obtain a level of quality suitable for preclinical use with consistent high synthesis yields. Radiochemical purity meets the pharmaceutical requirements, and it is maintained 4 h for 68Ga-DOTA-NT and 48 h for 177Lu-DOTA-NT. Extensive in vitro studies were conducted to assess the uptake and retention of 68Ga-DOTA-NT, the amount of non-specific binding of neurotensin and the effect of 177Lu-DOTA-NT on HT-29 cells. In vivo biodistribution of 68Ga-DOTA-NT revealed significant uptake at the tumour site, along with fast clearance evidenced by decreasing activity in kidneys and blood after 60 min p.i. 177Lu-DOTA-NT exhibited similar uptake in the tumour, but also a significant uptake at 14 days p.i. in the bone marrow was reported. These results successfully demonstrated the potential of neurotensin to deliver imaging/therapeutic 68Ga/177Lu radioisotopes pair, but also the need for further evaluation of the possible radiotoxicity effects on the liver, kidneys or bone marrow.

Role of Adiponectin and Tumor Necrosis Factor-Alpha in the Pathogenesis and Evolution of Type 1 Diabetes Mellitus in Children and Adolescents.

Type 1 diabetes mellitus (T1DM) is a complex condition caused by the destruction of pancreatic beta cells by autoimmune mechanisms. As a result, insulin deficiency and subsequent hyperglycemia occur. The aim of the present study is to investigate the role of adiponectin and tumor necrosis factor alpha (TNF-α) in the development of T1DM. The study is designed as an observational case-control study, involving 52 diabetic patients and 66 controls. Z scores for Body Mass Index (BMI), weight, height, and adiponectin and TNF-α serum levels were assessed in both groups. The T1DM group had significantly higher TNF-α levels and a significantly higher proportion of high-risk patients for inflammation based on TNF-α values as compared to the control group, while both groups had statistically similar adiponectin levels and a similar proportion of high/medium-risk patients based on adiponectin values. TNF-α plays a significant role in the pathogenesis and evolution of T1DM and it may represent an additional marker of disease progression, as well as a potential target of immunotherapeutic strategies. In the present study, no statistically significant differences were recorded in adiponectin levels neither in diabetic patients and controls, nor in high/medium severity risk diabetic patients.

Helicobacter pylori Gastritis in Children-The Link between Endoscopy and Histology.

BACKGROUND: The management of Helicobacter pylori (H. pylori) infection raises important challenges, still being the most common chronic infection worldwide in all age groups. In high-prevalence regions, paediatric patients need a specific focus, as the acquisition of the infection takes place in childhood. The objective of this study was to analyze the endoscopic and histopathologic changes of the gastric mucosa in H. pylori infected children. MATERIAL AND METHODS: A retrospective study was performed on consecutive paediatric patients, ranging from 0 to 18 years of age, who underwent an upper gastrointestinal endoscopy (UGE) for a period of 5 years, regardless of their symptomatology. Endoscopy reports and histological slides were reviewed and clinical, endoscopic, and histologic data were recorded. RESULTS: A total of 248 patients were included in the study, 82 (33.06%) of them being H. pylori infected. There was no difference in age and symptoms between the infected and noninfected group. A significant association was found between the H. pylori infection and histopathological parameters such as acute and chronic inflammatory infiltrate. The bacterial load influences the intensity of inflammation (p < 0.001). The chronic inflammation was predominant, only 23.2% of the patients displayed acute inflammation (p < 0.0001). The topographic distribution of inflammation was dominated by pangastritis (p = 0.04) with 58.6% of the patients presenting similar degrees of inflammation both in the antrum and corpus. CONCLUSION: Endoscopic features such as nodularity of the antral mucosa (p < 0.05) along with histological findings as lymphoid follicles (p < 0.05) are suggestive of H. pylori infection. However, the concordance between the endoscopic and histological diagnosis is still far from perfect (Cohen's k coefficient = 0.42), maintaining the need for an invasive approach in children.

The Role Of Adiponectin, TNF-α And Glutathione In The Pathogenesis And Evolution Of Type 1 Diabetes.

INTRODUCTION: Type 1 diabetes (T1DM) is a chronic autoimmune or idiopathic condition, featuring complex and unique interactions between proteins and enzyme systems. The purpose of the present study is to investigate the role of AdipoQ +276G>T, TNF-α-308G>A, GSTT1/GSTM1 polymorphic variants in the development of T1DM. MATERIALS AND METHODS: The study is designed as a cross-sectional study, involving 72 diabetic cases and 90 controls. Genotyping was carried out according to specific protocols for the above-mentioned polymorphic variants. RESULTS: The G allele of AdipoQ was associated with the development of type 1 diabetes (OR 0.577, CI95% 0.336-0.802, p=0.001), similar to the GG and GA genotypes (OR 0.405, CI95% 0.156-0.654, p=0.001 and OR 0.623, CI95% 0.401-0.855, p=0.004). The G allele of TNF-α was marginally associated with the development of type 1 diabetes (OR 0.789, CI95% 0.579-0.956, p=0.005). The presence of the T1 genotype was a strong predictor for type 1 diabetes (OR 3.4, CI95% 1.433-6.243, p<0.001). CONCLUSION: The results of our study suggest that G alleles of AdipoQ and TNFα act as a protective factor in T1DM, while the T1 allele for GST could be considered a risk factor for the development of Type 1 diabetes in our study group.