Development of Evaluation of Molecular Imaging Agents for Inflammation and Cancer

Xiao, Li, Department of Chemistry, University of Virginia
Pu, Lin, Department of Chemistry, University of Virginia
Pan, Dongfeng, Department of Radiology, University of Virginia
Demas, James, Department of Chemistry, University of Virginia
McGarvey, Glenn, Department of Chemistry, University of Virginia
Chruma, Jason

Molecular imaging is a technique to target a specific tissue or cell type using an imaging agent to provide non-invasive and direct visualization and characterization of in vivo biological processes at cellular and molecular level. The intrinsic tissue/cell characteristics act as in vivo target and against which the target-specific molecular imaging agent provides signal source that could be detected by various imaging modalities, such as optical imaging (fluorescence and bioluminescence), positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and ultrasound, etc. Various imaging techniques are often more complementary than competitive. The choice for an imaging modality or combination of techniques is mainly determined by the specific biological question to be addressed. Moreover, many other factors are to be considered, such as efficiency of detection in a timely manner, cost ease of benefits, and availability of tools and instruments. In this dissertation, studies involving development and evaluation of a series of peptide and antibody based imaging agents for non-invasive detection of inflammation are described. These imaging agents are designed and synthesized to target physiologically important receptors (e.g. formyl peptide receptor) on surfaces of leukocytes (e.g. neutrophil) for various imaging modalities, such as near-infrared fluorescence (NIRF) imaging, SPECT and PET. In vitro and in vivo evaluation studies of these imaging agents under inflammatory and non-inflammatory conditions are successfully performed, including partition coefficient, target-specificity, blood kinetics, biodistribution, imaging feasibility in various animal models and immunohistochemical ii analysis. Highly promising results obtained from these studies suggest the potential of these imaging agents to advance into further pre-clinical and clinical research. In addition to developing molecular imaging agents for inflammation, a tumorspecific heptamethine cyanine-based dual-modality PET/NIRF imaging agent is being investigated for cancer imaging. Data obtained from this proof-of-concept study, such as spectroscopic evaluation, tumor-specific cellular-uptake, biodistribution, blood kinetics, NIRF and nuclear imaging are highly encouraging. Initial results from these studies set a solid foundation for developing a new generation of tumor-specific agents to enable early detection, targeted therapy and simultaneous monitoring of treatment efficacy of cancers.

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PHD (Doctor of Philosophy)
molecular imaging, cells, tissue
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