α-synuclein monoclonal antibodies in Parkinson's disease: A failed promise or unmet potential?

2559 Background: Immune checkpoint immunotherapies (ICI) have transformed cancer treatment, but patients have varied responses and potential risks of autoimmune disease. To improve ICI, we need to identify biomarkers to select responding patients and research new approaches. To this, resident memory T cells (TRM) LT CD8 + CD103 + , have been identified as a promising tumor-specific biomarker for studying therapeutic efficacy involving ICI. Internal radiotherapy appears to be a promising approach. Our objective is to develop new therapeutic approaches combining radiotherapy and ICI (radioimmunotherapy) using CD8 + CD103 + immunoPET imaging as a predictive biomarker of efficacy. Methods: After developing and characterizing a new CD103 radiotracer and validating the dual 18 F PET-Scan imaging for CD8 + and CD103 + in C57BL/6 mouse models, we implanted mice subcutaneously with MC38 and othotopically syngenetically with LLC. We evaluated the efficacy of radioimmunotherapy vs ICI and the predictive effect of TRM in this syngeneic orthotopic model. To this, we implanted two syngeneic NSCLC cell lines, either LLC for a cold tumor or CMT167 for a warmer tumor. We performed double imaging prior to treatment with [ 18 F]-CD8 mutated FcRn and [ 18 F]-CD103 minibody on 2 consecutive days. We treated our mice 3 times, 3 days apart, with the first dose of either cold Avelumab or [ 177 Lu]-Avelumab (8MBq). The second and third doses were cold Avelumab. We performed double post-treatment imaging with [ 18 F]-CD8 mutated FcRn and [ 18 F]-CD103 minibody on 2 consecutive days, as well as ex vivo analyses and a survival study. Results: There was a trend towards improved survival in [ 177 Lu]-Avelumab treated mice vs Avelumab treated mice but more markedly in the immunogenic model (30d vs 21d). The impact on tumor growth was assessed by comparing the two treatment groups with untreated mice. Radioimmunotherapy induced a significant decrease in overall tumor growth compared with mice treated with ICI (0.45 ccm vs 0.68 ccm, *p < 0.05 turkey's multiple comparison test) in the immunogenic model. In the cold tumor model, there was a significant difference in the tumor size ratio before and after treatment, for mice treated with radioimmunotherapy vs ICI (12.96 vs 26.08, ***p < 0.001 Uncorrected Fisher's LSD). An increase in immune infiltration was validated by PET and flow cytometry for the immunogenic model (pre-treatment: 5.00%ID/cc max, versus post-treatment 8.23%ID/cc max for CD8, *p < 0.05 two way-Anova). More heterogeneous results were observed in the cold tumor model. Conclusions: Radio-immunotherapy reduces tumour growth and stimulates the immune system by circulating LT CD8 . The dual 18 F PET-Scan imaging for CD8 + and CD103 + offer a promising non-invasive visualization of tumor-infiltrating CD103 + TRMs. We need to correlate LT CD8+ /CD103+ infiltration with therapeutic response.

Interest is growing in the potential role of manganese (Mn) in Alzheimer’s Disease (ADRD). This nested pilot study of a ferroalloy workers cohort was aimed to investigate the effects of long-term occupational Mn exposure on cognitive function through β-amyloid (Aβ) modification and brain deposition, as well as metabolomic, lipidomic and proteomic profiling. We examined 6 male exposed workers (median age 63, exposure duration 31 yrs), and 5 historical controls (median age 60) who had undergone brain PET scan imaging showing higher Aβ deposition among the exposed compared to the controls (p < 0.05). The average annual cumulative respirable Mn of the ferroalloy workers was 329.23 ± 516.39 μg/m3 (geometric mean 118.59). Average Mn level in plasma of the exposed subjects (0.704 ± 0.2 ng/mL) was significantly higher than the controls (0.397 ± 0.18). Pathway analyses using LC-MS/MS results revealed impacted metabolomic pathways such as olfactory signaling, mitochondrial fatty acid beta-oxidation, biogenic amine synthesis, SLC-mediated transmembrane transport, and glycerophospholipid and choline metabolism in the Mn exposed group. Single molecule arrays (Simoa) analysis revealed notable modifications of AD-related plasma biomarkers; protein microarray (chip) showed significant changes (p < 0.05) in the levels of some plasma antibodies targeting autoimmune and neuronal associated proteins such as Aβ (25–35), GFAP, Serotonin, Human NOVA1, and Human Siglec-1/CD169 among the Mn exposed individuals. This data provides evidence on Mn-induced alterations of pathways and biomarkers associated with cognitive neurodegenerative diseases.

Abstract Background To cope with the increasing number of infected patients, medical access was restricted, and public facilities were closed throughout the COVID-19 pandemic. Early detection and treatment of esophageal cancer is critical for improved prognosis. However, the impact of pandemic-related medical access restrictions has not be evaluated to date for esophageal cancer. Therefore, the purpose of this research is to determine how the lockdown policy affected the surgical outcome of patients with esophageal cancer. Methods We analyzed patients who underwent esophagectomy for esophageal cancer between 2016-2022 using data obtained from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), including the procedure targeted esophagectomy database. The patients were stratified into two groups based on their operation date relative to pandemic (BEFORE COVID group: 2016-2019 vs AFTER COVID group: 2020-2022). Demographic data and perioperative outcomes were compared between the two groups. Statistical analysis included Chi-square tests for categorical variables and independent student T-tests for continuous data, with a significance threshold set at p &amp;lt; 0.05. Results Between 2016-2022, 7,198 esophageal cancer patients underwent esophagectomy. Clinical T4 increased significantly, but clinical N and pathologic T and N stages showed no impact. PET scan imaging, neoadjuvant chemotherapy and radiotherapy remained unchanged. The utilization of a minimally invasive approach rose substantially from 32.6% to 47.2% (p &amp;lt; 0.001). Positive margin rates increased from 7.5% to 9% (p = 0.03), and anastomotic leak rates increased from 14.1% to 17.2% (p &amp;lt; 0.001). Operative time, blood loss, and conversion rate showed no significant differences. Perioperative complications, including organ space surgical site infections and myocardial infarctions, significantly increased after COVID-19. Conclusion The COVID-19 pandemic altered the clinical staging of esophageal cancer patients undergoing esophagectomy, but it did not disrupt access to essential investigations and treatment. A notable increase in the implementation of minimally invasive techniques was observed after the pandemic. However, significant impacts were noticed on operative outcomes, including positive margin and leak rates.

Pyramid-attentive GAN for multimodal brain image complementation in Alzheimer’s disease classification

Abstract #1393024: A Rare Case of ACTH-Producing Pituitary Carcinoma in Nelson’s Syndrome

Introduction: Sometimes, a patient receives a poor quality medical image from a medical imaging center. Which the doctor orders to re-image with a drug contrast media agent. At this time, practical action is challenging to provide a proper image. Cobalt oxide nanoparticles show different activities based on different sizes and shapes. Objectives of this project is achievement a critical size of cobalt oxide nanoparticles between 5 to 10 nanometers for easy circulation in the blood and Investigation of the effect of cobalt oxide nanoparticles on the quality of CT from laboratory mice(Mus musculus).Material and Methods: In this study, the coupling method was used to prepare the cobalt oxide nanoparticles. Co3O4 nanoparticle coatings are used for this purpose. They were investigated through the Fourier-transform infrared (FTIR) analysis, X-rays diffraction (XRD). In order to investigate the efficacy of cobalt oxide nanoparticles, we injected a suspension into the Mus musculus, and then the computerized tomography (CT) scans were taken before and after injection of the nanoparticles. Then, quantity evaluation was performed using the calculating the average local contrast media of the whole image.Results: The average size of cobalt oxide nanoparticles was obtained about 5.8 nm, which is an appropriate size in the nanometer scale. After injecting of cobalt oxide nanoparticles into the mice and then CT scan imaging, we have obtained a better clarity.Conclusion: Cobalt oxide nanoparticles behave well for use as a pharmacological contrast media agent in CT scan imaging.

Combined Genotype Analysis of Tumor and Cell-Free DNA By Ultra-Deep Targeted Sequencing: Correlation with PET-Scan Imaging in a Prospective Cohort of Diffuse Large B-Cell Lymphoma Patients

Abstract Background: The differential diagnosis of adrenal incidentalomas is broad and includes benign or malignant primary adrenal lesions, metastases, myelolipomas, infections or hemorrhage. We present here a patient with a gastrointestinal stromal tumor (GIST) presenting as an adrenal incidentaloma. Clinical Case: A 64-year-old man was referred to Endocrinology for the work-up of a left adrenal incidentaloma discovered on an abdominal CT scan performed for left upper quadrant abdominal pain. His past medical history included well-controlled type 2 diabetes and hypertension. On subsequent imaging, the mass was described as a solid homogenous nodule with a density of 31 HU and an absolute contrast washout of 22%. Between 2017 and 2020, the mass’ size increased from 14 x 13 to 24 x 19 millimeters. Further functional imaging revealed no 131I-MIBG uptake but moderate hypermetabolism on FDG PET-CT with a SUVmax of 4.5. There was discordance regarding the mass’ localization between the various imaging modalities used preoperatively: some showed a left adrenal lesion whereas others suggested that it was adjacent to, but distinct from, the adrenal gland. Biochemical workup included normal 1-mg dexamethasone suppression test, serum potassium levels, 24-hour urine fractionated catecholamines, as well as plasma free metanephrines and normetanephrines. Chromogranin A levels were also normal. In light of these findings, laparoscopic tumor resection, with or without left adrenalectomy, was scheduled. During surgery, it was discovered that the tumor was intraperitoneal, located next to the splenic hilum and originating from the greater curvature of the stomach; a partial gastrectomy was therefore performed, without left adrenalectomy. Pathological evaluation revealed that the mass was a small spindle cell-type GIST. Genetic analysis of the tumoral DNA showed a somatic mutation in exon 11 of the KIT gene (c.1658_1669del, p.Tyr553_Gln556del). Conclusion: We report a rare case of gastric GIST initially mimicking a left adrenal incidentaloma. Localization of GISTs in the adrenal area is rare, with very few cases reported to date in the literature. Unlike other cases described previously, our patient underwent the right procedure thanks to adequate tumor localization during surgery. However, as some patients have experienced unnecessary adrenalectomy for similar clinical presentations, gastric GISTs should be kept in mind in the differential diagnosis of non-functional atypical adrenal masses, especially in the presence of suspicious PET scan imaging.

A new product development (NPD) process consists of a sequence of events that create, model and implement an idea. All of these processes share some common stages necessary to ensure a successful new product launch. An interdisciplinary team was tasked with executing the initial phases of the NPD process for a start-up. This paper presents an exploratory case study following their journey of development of a novel application involving a MEMS accelerometer, typically used in seismic sensing, to improve PET scan imaging for medical diagnostics. Their work is interpreted with the theoretical stages mentioned in the literature and insights are drawn from the design thinking and validation methods used by this team. The effectiveness of these methods as perceived independently by each team member is also analysed. The criteria used for screening possible applications during the entire process are presented and an evaluation of their effectiveness and relevance is conducted.

From a liquid biopsy, cell-free DNA (cfDNA) can provide information regarding basal tumoral genetic patterns and changes upon treatment. In a prospective cohort of 30 diffuse large B-cell lymphomas (DLBCL), we determined the clinical relevance of cfDNA using targeted next-generation sequencing and its correlation with PET scan imaging at the time of diagnosis and during treatment. Using a dedicated DLBCL panel, mutations were identified at baseline for 19 cfDNAs and profiles were consistent with expected DLBCL patterns. Tumor burden-related clinical and PET scan features (LDH, IPI, and metabolic tumor volume) were significantly correlated with the quantity of tumoral cfDNA. Among the four patients presenting additional mutations in their cfDNAs, three had high metabolic tumor volumes, suggesting that cfDNA more accurately reflects tumor heterogeneity than tissues biopsy itself. Mid-treatment, four patients still had basal mutations in their cfDNAs, including three in partial response according to their Deauville scores. Our study highlights the major interests in liquid biopsy, in particular in the context of bulky tumors where cfDNA allows capturing the entire tumoral mutation profile. Therefore, cfDNA analysis in DLBCL represents a complementary approach to PET scan imaging.

Classic Hodgkin lymphoma (HL) involving the endometrium is extremely rare as lymphoma involving the female genital tract is uncommon in general and those that do are most commonly non-Hodgkin lymphomas. Here, we present a patient with refractory classic HL where PET scan imaging results led to an endometrial biopsy that confirmed uterine involvement of her disease.

We evaluated the effect of adding docosahexaenoic:arachidonic acids (3:2) (DHA+ARA) to 2 representative commercial infant formulas on brain activity and brain and eye lipids in an artificially reared rat pup model. The formula lipid background was either a pure plant oil blend, or dairy fat with a plant oil blend (1:1). Results at weaning were compared to breast milk-fed pups. Brain functional activity was determined by positron emission tomography scan imaging, the brain and eye fatty acid and lipid composition by targeted and untargeted lipidomics, and DHA brain regional location by mass-spectrometry imaging. The brain functional activity was normalized to controls with DHA+ARA added to the formulas. DHA in both brain and eyes was influenced by formula intake, but more than two-thirds of tissue DHA-glycerolipids remained insensitive to the dietary challenge. However, the DHA lipidome correlated better with brain function than sole DHA content ( r = 0.70 vs. r = 0.48; P < 0.05). Brain DHA regional distribution was more affected by the formula lipid background than the provision of PUFAs. Adding DHA+ARA to formulas alters the DHA content and lipidome of nervous tissue in the neonate, making it closer to dam milk-fed controls, and normalizes brain functional activity.-Aidoud, N., Delplanque, B., Baudry, C., Garcia, C., Moyon, A., Balasse, L., Guillet, B., Antona, C., Darmaun, D., Fraser, K., Ndiaye, S., Leruyet, P., Martin, J.-C. A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.

Esophageal cancer, the sixth most common cause of cancer globally, is characterized by the development of early systemic metastatic disease. Adenocarcinoma of the esophagus and gastroesophageal junction (GEJ) is more common in the West. Preoperative chemotherapy or chemoradiotherapy is employed for locally advanced disease with contemporary studies suggesting higher rates of curative resection and reduced rates of local recurrence with the combination of chemotherapy and radiation therapy given prior to surgery. The role of targeted agents and PET scan imaging in preoperative therapy is under active investigation.

Auditory Brain Development in Children with Hearing Loss – Part Two

Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting.

Tatouages et imagerie médicale : problèmes et mythes

(18)F-Fluorocholine (FCH) and (11)C-acetate (ACE) PET are widely used for detection of recurrent prostate cancer (PC). We present the first results of a comparative, prospective PET/CT study of both tracers evaluated in the same patients presenting with recurrence and low PSA to compare the diagnostic information provided by the two tracers. The study group comprised 23 patients studied for a rising PSA level after radical prostatectomy (RP, 7 patients, PSA ≤ 3 ng/ml), curative radiotherapy (RT, 7 patients, PSA ≤ 5 ng/ml) or RP and salvage RT (9 patients, PSA ≤ 5 ng/ml). Both FCH and ACE PET/CT scans were performed in a random sequence a median of 4 days (range 0 to 11 days) apart. FCH PET/CT was started at injection (307 ± 16 MBq) with a 10-min dynamic acquisition of the prostate bed, followed by a whole-body PET scan and late (45 min) imaging of the pelvis. ACE PET/CT was performed as a double whole-body PET scan starting 5 and 22 min after injection (994 ± 72 MBq), and a late view (45 min) of the prostate bed. PET/CT scans were blindly reviewed by two independent pairs of two experienced nuclear medicine physicians, discordant subgroup results being discussed to reach a consensus for positive, negative end equivocal results. PET results were concordant in 88 out of 92 local, regional and distant findings (Cohen's kappa 0.929). In particular, results were concordant in all patients concerning local status, bone metastases and distant findings. Lymph-node results were concordant in 19 patients and different in 4 patients. On a per-patient basis results were concordant in 22 of 23 patients (14 positive, 5 negative and 3 equivocal). In only one patient was ACE PET/CT positive for nodal metastases while FCH PET/CT was overall negative; interestingly, the ACE-positive and FCH-negative lymph nodes became positive in a second FCH PET/CT scan performed a few months later. Overall, ACE and FCH PET/CT showed excellent concordance, on both a per-lesion and a per-patient basis, suggesting that both tracers perform equally for recurrent prostate cancer staging.

An exploratory study of the relationship of symptom domains and diagnostic severity to PET scan imaging in borderline personality disorder

T lymphocytes play an important role in mechanisms of immunological tolerance, where they contribute to tumor suppression activities. To determine the effects of surgical intervention on T cell status, a group of 21 patients with small cell lung cancer [NDRP], 13 of whom had confirmed lesions and 8 without who served as controls. The size and mass of all tumors were confirmed by MRI and PET scan imaging with Glu18 isotope enrichment. Measures of CD4/CD25 T cells before and after therapy resulted in a return toward normal of circulating T cell concentrations, consistent with a normalization of the expression and function of T lymphocytes after tumor reduction. These results suggest that the monitoring of circulating T cell populations may serve as viable indicators of treatment effectiveness for NDRP treatment. Institutional Support.