title: Targeted noninvasive imaging of EGFR-expressing orthotopic pancreatic cancer using multispectral optoacoustic tomography.
abstract: Detection of orthotopic xenograft tumors is difficult due to poor spatial resolution and reduced image fidelity with traditional optical imaging modalities. In particular, light scattering and attenuation in tissue at depths beyond subcutaneous implantation hinder adequate visualization. We evaluate the use of multispectral optoacoustic tomography (MSOT) to detect upregulated epidermal growth factor (EGF) receptor in orthotopic pancreatic xenografts using a near-infrared EGF-conjugated CF-750 fluorescent probe. MSOT is based on the photoacoustic effect and thus not limited by photon scattering, resulting in high-resolution tomographic images. Pancreatic tumor-bearing mice with luciferase-transduced S2VP10L tumors were intravenously injected with EGF-750 probe before MSOT imaging. We characterized probe specificity and bioactivity via immunoblotting, immunocytochemistry, and flow cytometric analysis. In vitro data along with optical bioluminescence/fluorescence imaging were used to validate acquired MSOT in vivo images of probe biodistribution. Indocyanine green dye was used as a nonspecific control to define specificity of EGF-probe accumulation. Maximum accumulation occurred at 6 hours postinjection, demonstrating specific intratumoral probe uptake and minimal liver and kidney off-target accumulation. Optical bioluminescence and fluorescence imaging confirmed tumor-specific probe accumulation consistent with MSOT images. These studies demonstrate the utility of MSOT to obtain volumetric images of ligand probe biodistribution in vivo to detect orthotopic pancreatic tumor lesions through active targeting of the EGF receptor.
authors.affiliation: Department of Medicine, University of Louisville, Kentucky.
authors.forename: Shanice V
authors.initials: SV
authors.lastname: Hudson
authors.affiliation: Department of Medicine, University of Louisville, Kentucky.
authors.forename: Justin S
authors.initials: JS
authors.lastname: Huang
authors.affiliation: Department of Medicine, University of Louisville, Kentucky.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Yin
authors.affiliation: Department of Medicine, University of Louisville, Kentucky.
authors.forename: Sabrin
authors.initials: S
authors.lastname: Albeituni
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Kentucky.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rush
authors.affiliation: Department of Medicine, University of Louisville, Kentucky.
authors.forename: Anil
authors.initials: A
authors.lastname: Khanal
authors.affiliation: Department of Medicine, University of Louisville, Kentucky.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Kentucky.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Ceresa
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Kentucky. Department of Bioengineering, University of Louisville, Kentucky.
authors.forename: Hermann B
authors.initials: HB
authors.lastname: Frieboes
authors.affiliation: Department of Medicine, University of Louisville, Kentucky. Department of Pharmacology and Toxicology, University of Louisville, Kentucky. lrmcna01@louisville.edu.
authors.forename: Lacey R
authors.initials: LR
authors.lastname: McNally
mesh_terms: D000818:Animals; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000302:isolation & purification; D005456:Fluorescent Dyes; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D061088:Photoacoustic Techniques / Q000379:methods*; D011859:Radiography; D014054:Tomography / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D005456:Fluorescent Dyes; C512478:EGFR protein, human; D066246:ErbB Receptors