Nanomaterial-Enhanced Positron-Emission Tomography Imaging and Targeted Drug Delivery

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  • NFRF Exploration awarded in 2020: Positron Emission Tomography (PET) is among the most sophisticated in vivo imaging modalities using radioactive isotopes that decay by positron emission. PET is non-invasive, painless, and hence patient friendly; provides full-depth images of the human body featuring dynamic space and time resolution of injected radio-labeled diagnostics (e.g. for cancer and neuro-imaging); and offers unprecedented detection sensitivity. PET radionuclides attached to bio-molecules or nano-materials (e.g., nanogels) follow the biodistribution of these compounds for disease staging, therapy, and/or biodistribution mapping. The latter feature is important to follow the in vivo dispersal of radio-labeled nanogels intended to deliver a therapeutic payload encapsulated within the nanogel structure to a tumor location. If loaded nanogels are injected into a cancer patient without the ability to understand their biodistribution (and accumulation near tumor sites), then an adequate assessment of their time-dependent therapeutic delivery cannot be obtained, thus hampering drug development. Only when the accumulation is high enough should the therapeutic payload be released by external stimulation/manipulation (e.g. radiation induced heating).

    Our multidisciplinary team aims to develop radiolabeling protocols to chemically introduce fluorine-18 to chemotherapeutic-loaded nanogels by a simple one-step labeling procedure based on three noncanonical labeling methodologies: 1) the SiFA strategy which was developed by the Schirrmacher group and has now found its first human clinical application for in vivo tumor imaging (First-in-human 18FSiFAlin-TATE PET/CT for NET imaging and theranostics, IMAGE OF THE MONTH, lhan, H. et al Eur J Nucl Med Mol Imaging (2019); 2) the BF3 isotopic exchange labeling strategy (Perrin et al); and 3) the Al[18F]F chelation chemistry (Goldenberg et al). These labeling strategies will be applied to introduce the isotope18F into the nanogel structure to follow their bio-distribution in vivo in a cancer animal model using small animal micro PET imaging. Nanogels will be used to “hold” the therapeutic payload, as they have a large free volume that can be used as a reservoir. The kinetics of the loaded/un-loaded nanogels’ biodistribution within tumor bearing animals will be accurately assessed by acquiring temporal dynamic PET images to prove that 18F-labeled nanogels can serve as delivery shuttles for tumor therapy.

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    Research Material
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    ©️Serpe, Michael J. All rights reserved other than by permission. This document embargoed to those without UAlberta CCID until 2030.