Dr. Wilks’s poster was a finalist in the “Oncology: Basic, Translational & Therapy Track” and presented “Nanoparticle-Based PET Imaging of T-cell Trafficking in Immuno-Competent Murine Tumor Models”. Below is a summary of his work.
Due to the increased interest and development of immunotherapies in oncologic applications, there is an increased need for non-invasive & quantitative measures of immune trafficking and localization. Current methods for imaging of inflammation have several serious limitations, such as the lack of specificity to the type of inflammatory response (as seen in WBC-SPECT) or to metabolically active but non-inflamed tissues (as in FDG-PET). Previously, we demonstrated that the FDA-approved nanoparticle drug Feraheme (FH) could be modified through click chemistry to include a cell-penetrating peptide (protamine), and radiolabeled to allow for quantitative imaging through PET. These nanoparticles (89Zr-Prot-FH) can be used for ex vivo labeling of specific cell populations, which can be re-injected to monitor the trafficking of these cells. Here, we apply this technology to T-cell trafficking in an immuno-competent murine cancer model.
Yuan, Wilks, El Fakhri, Normandin, Kaittanis, & Josephson. “Heat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials”. PloS one. 2017;12(2)
Maximum intensity sagittal projections in representative mice 144h after injection with free NP (top) or ex vivo labeled cells (bottom). Much higher splenic activity was seen in cell-injected mice (red arrows), while higher hepatic uptake was seen in NP-injected mice (green arrows). Little tumor activity was seen in either cohort (blue arrows).
Signal is shown relative to activity measured immediately before drug treatment. Rapid and reversible mobilization is seen immediately following drug challenge (black bars).
Dr. Wu’s poster was a finalist in the “Cardiovascular Track” and presented “Detection of early atherosclerotic plaques with TLR4-conjugated zwitterionic near-infrared fluorophore: a pilot mice study”. Below is a summary of his work.
Atherosclerosis is a major contributor to heart disease. Early detection of high-risk plaques can improve patient outcomes. We propose non-invasive near-infrared fluorescence (NIRF) imaging with toll-like receptor 4 (TLR4)-conjugated zwitterionic NIR flurophore (ZW800-1C) targeting macrophage TLR4 to aid in locating such plaques.
NIR fluorescence could be detected in the chest region of atherosclerotic mice injected with TLR4-ZW800-1C with a signal to baseline ratio of 2.00±0.72, 1.91±0.92 and 1.77±0.66 at 4, 8, and 24 hours, respectively. Ex-vivo images of the aortic arch showed a localized region of fluorescence.
A. White and 760 nm light NIRF image of TLR4-ZW800-1C.
B. White and 760 nm images of mouse at baseline, 4, 8, and 24 hours.
C. Signal to background at the four time points
D. Photo of NIRF imaging system
E. White and 760 nm of ex-vivo heart
All animal experiments were performed under anesthesia according to an MGH institutional animal care and use committee-approved protocol.