Comparison of HP and LH derivatives revealed that fractionated smaller heparin has greater anti-inflammatory activity. The degree of sulfation appeared to be important in determining their anti-inflammatory activity, which would correspond to previous results using the derivatives of site-selectively desulfated HP. The IC 50 value for suppression of TNF-α production from the macrophages was the smallest with the derivative of LH, followed by HP, CS, and HA. All of the conjugates formed self-assembled nanoparticles in aqueous solution. We newly synthesized the stearylamine conjugates of chondroitin sulfate (CS), hyaluronic acid (HA), and low-molecular-weight heparin (LH), and investigated the effect of the position and degree of sulfation and molecular weight of GAGs on their anti-inflammatory activity. Sellmyer Using CD69 PET Imaging to Monitor Immunotherapy-Induced Immune Activation. Join Facebook to connect with Babazadeh Hasan and others you may know. Considering that HP is not the only GAG to have anti-inflammatory activity, the present study was initiated to examine whether conjugation of GAGs with aliphatic amines is generally effective in their activity augmentation against LPS-stimulated macrophages. Edwards, Bryan Chang, Hasan Babazada, Katheryn Lohith, Daniel H. View the profiles of people named Babazadeh Hasan. Facebook gives people the power to share and makes the world more open and connected. We previously revealed that glycol-split heparin (HP)-aliphatic amine conjugates form self-assembled nanoparticles and suppress the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in lipopolysaccharide (LPS)-stimulated macrophages much more strongly than native HP (J. Join Facebook to connect with Hassan Babazada and others you may know. Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.Glycosaminoglycans (GAGs) play important roles in various biological processes such as cell adhesion and signal transduction, as well as promote anti-inflammatory activity.Hassan,Yousuf ( ) - GM Bok,B (2624) 0-1, Midwest Collegiate Blitz. In three patients with advanced melanoma or hepatocellular carcinoma on immunotherapy, post-treatment CD8 PET/CT scans demonstrated increased 89Zr-Df-IAB22M2C uptake in tumor lesions, which correlated with response.Ĭonclusion: CD8 PET imaging with 89Zr-Df-IAB22M2C is safe and has the potential to visualize the whole-body biodistribution of CD8+ leukocytes in tumors and reference tissues, and may predict early response to immunotherapy. GM Bok,B (2616 ) - FM Babazada,Khazar (2431) 0-1, Titled Tue 17th May Late. Radiotracer uptake in tumors was noted in 10/15 subjects, including 7/8 subjects on immunotherapy, 1/2 subjects on targeted therapy, and 2/5 treatment naïve subjects. spleen, bone marrow, nodes) with maximum uptake at 24-48 hours post injection and low background activity in CD8-poor tissues (e.g. 89Zr-Df-IAB22M2C accumulated in tumors and CD8-rich tissues (e.g. No drug-related adverse events or abnormal laboratory results were noted except for a transient increase in anti-drug antibodies in 1 subject. Results: 15 subjects with metastatic melanoma, non-small cell lung cancer, and hepatocellular carcinoma were enrolled. Biodistribution, radiation dosimetry, and semi-quantitative evaluation of 89Zr-Df-IAB22M2C uptake were performed in all patients.
A two-stage design included a dose-escalation phase and a dose-expansion phase.
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Patients received 111 MBq of 89Zr-Df-IAB22M2C followed by serial PET scans over a 5-7-day period. Methods: We conducted a phase 1 first-in-human PET imaging study using an anti-CD8 radiolabeled minibody, 89Zr-Df-IAB22M2C, to detect whole body and tumor CD8+ leukocyte distribution in patients with metastatic solid tumors. This study was designed to optimize conditions for performing CD8 PET imaging with 89Zr-Df-IAB22M2C and determine if CD8 PET imaging could provide a safe and effective non-invasive method of visualizing the whole body biodistribution of CD8+ leukocytes. Such imaging probes could be used to predict early response to cancer immunotherapy, help select effective single or combination immunotherapies, and facilitate the development of new immunotherapies or immunotherapy combinations. There is a need for in vivo diagnostic imaging probes that can noninvasively measure tumor infiltrating CD8+ leukocytes.
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