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393 Objectives: The currently available PET tracers i.e. 18F-FET and 11C-methionine have proven high diagnostic efficacy in GBM. However, the development of SPECT based tracers is always viewed as a cost-effective alternate to PET imaging. The aim of the present study was to determine the diagnostic efficacy of 99mTc-labelled MDM (bis-methionine) SPECT in the diagnostic work up in glioma. Methods: The present study was conducted in 143 glioma patients (101M: 42F; mean age 41.97±11.9 years; range 18-71 years) who were newly diagnosed or previously treated or who were recruited for post-surgical radiotherapy/chemotherapy treatment from December 2014 to August 2018. Amongst, 143 patients, 29/143 (20.0%) were freshly diagnosed patients of glioma and the remaining 114/143 (80.0%) patients were on post-surgery follow-up (radiological/clinical) with chemotherapy/radiotherapy interventions. The patients were subjected to a detailed histopathological tumor analysis (including Ki-67 index), 99mTc-MDM-SPECT, conventional MRI, DSCE-MRI and MR spectroscopy for the disease evaluation at presentation and during the course of follow-up after surgery/chemo/radiotherapy. A total of 227 brain scans (99mTc-MDM-SPECT) and an equal number of conventional MRI scans were performed in 143 patients. The results of the two imaging modalities were compared and correlated with the clinical findings. In a sub-set of patients (n=43), a quantitative DSCE-MRI and MR spectroscopy analysis was done. The results of the later were compared with the 99mTc-MDM-SPECT quantitative results for validation of this technique for accuracy in the glioma detection and characterization. Results: On histopathological analysis, 26/29 patients (pre-surgery group) were diagnosed to have glioma ( G IV-13; G III-04; G II-09) and the remaining 3/29 patients were found to be meningioma. The mean target to non-target (T/NT) ratios of 99mTc-MDM in glioma grade II, grade III, and grade IV patients were estimated to be 2.46±2.3, 7.13±2.2 and 5.16±1.2 respectively. This ratio was much higher (15.9 ±6.8) in meningioma. The ROC curve analysis derived cut-off value of T/NT ratio of greater than 3.08 when used to discriminate low grade from high grade glioma provided 100% sensitivity, 87.5% specificity. In the post-surgery group, the final diagnosis could be made in 72/114 patients. Out of these, 47/72 showed tumor recurrent (Fig.1) or residual disease and the remaining 25 patients showed necrosis. The ROC curve analysis derived cut-off value of T/NT ratio of greater than 1.90 used to discriminate tumor recurrence from necrosis offered sensitivity and specificity of 97.9 % and 92.0% respectively. A similar analysis on DSCE-MRI quantitative data with derived nCBV cut of value of greater than 3.32 for discriminating tumor recurrence versus necrosis provided sensitivity and specificity of 84.6% and 93.0% respectively. MR spectroscopy data analysis estimated the cut-of ratios; sensitivity/specificity of different metabolites i.e. Cho/NAA, Cho/Cr, Cr/NAA, Cr/Cho and Cho/LL to be >1.57, 81.0%/73.0%; >1.64, 85.3%/73.7%; >1.06. 57.1%/ 63.6%; ≤ 0.60, 72.3%/81.0% and >0.90, 71.4%, /50% respectively. T/NT ratio showed a strongest linear correlation with nCBV(r = 0.775, P

Interleukin-8 (IL-8, CXCL8) is a neutrophil chemotactic factor belonging to the family of chemokines. IL-8 was shown to resist pepsin cleavage displaying its high resistance to this protease. However, the molecular mechanisms underlying this resistance are not fully understood. Using our in-house database containing the data on three-dimensional arrangements of secondary structure elements from the whole Protein Data Bank, we found a striking structural similarity between IL-8 and pepsin inhibitor-3. Such similarity could play a key role in understanding IL-8 resistance to the protease pepsin. To support this hypothesis, we applied pepsin assays confirming that intact IL-8 is not degraded by pepsin in comparison to IL-8 in a denaturated state. Applying 1H-15N Heteronuclear Single Quantum Coherence NMR measurements, we determined the putative regions at IL-8 that are potentially responsible for interactions with the pepsin. The results obtained in this work contribute to the understanding of the resistance of IL-8 to pepsin proteolysis in terms of its structural properties.

Undeniable evidence shows that microglia in the spinal cord undergo marked reactions following peripheral injuries. However, only rare studies have investigated the possible short and long term microglial reaction in brain regions following peripheral nerve injury and its interspecies specificities. In the present study we examined microglia in subdivisions of the prefrontal cortex in mice and rats, 7 days and 42 days after spared nerve injury (SNI) of the sciatic nerve. We show that a bilateral increase of microglial density takes place in the infralimbic cortex in rats 7 days post-injury (sham vs. SNI, n = 5: ipsilateral 35.4% increase of the median, p = 0.0317; contralateral 24.9% increase of the median, p = 0.0079), without any detectable change in the other investigated regions, namely the anterior cingulate, prelimbic and agranular insular cortices. In mice, no observable difference could be found in any region at both time points, neither using Iba-1 immunostaining nor with CX3CR1-eGFP animals. Our results indicate that a transitory, species-specific and highly regionalized microglial reaction takes place in the prefrontal cortex following peripheral nerve injury.

Patients with metastatic medullary thyroid cancer (MTC) have limited systemic treatment options. The use of radiolabeled gastrin analogs targeting the cholecystokinin-2 receptor (CCK2R) is an attractive approach. However, their therapeutic efficacy is presumably decreased by their enzymatic degradation in vivo. We aimed to investigate whether the chemically stabilized analog