title: Tomography of epidermal growth factor receptor binding to fluorescent Affibody in vivo studied with magnetic resonance guided fluorescence recovery in varying orthotopic glioma sizes.
abstract: The ability to image targeted tracer binding to epidermal growth factor receptor (EGFR) was studied in vivo in orthotopically grown glioma tumors of different sizes. The binding potential was quantified using a dual-tracer approach, which employs a fluorescently labeled peptide targeted to EGFR and a reference tracer with similar pharmacokinetic properties but no specific binding, to estimate the relative bound fraction from kinetic compartment modeling. The recovered values of binding potential did not vary significantly as a function of tumor size (1 to 33 mm3), suggesting that binding potential may be consistent in the U251 tumors regardless of size or stage after implantation. However, the fluorescence yield of the targeted fluorescent tracers in the tumor was affected significantly by tumor size, suggesting that dual-tracer imaging helps account for variations in absolute uptake, which plague single-tracer imaging techniques. Ex vivo analysis showed relatively high spatial heterogeneity in each tumor that cannot be resolved by tomographic techniques. Nonetheless, the dual-tracer tomographic technique is a powerful tool for longitudinal bulk estimation of receptor binding.
authors: Dartmouth College, Department of Physics & Astronomy, Hanover, New Hampshire 03755, United States.
authors: Robert W
authors: RW
authors: Holt
authors: Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire 03755, United States.
authors: Jennifer-Lynn H
authors: JL
authors: Demers
authors: Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire 03755, United States.
authors: Kristian J
authors: KJ
authors: Sexton
authors: Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire 03755, United States.
authors: Jason R
authors: JR
authors: Gunn
authors: Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire 03755, United States.
authors: Scott C
authors: SC
authors: Davis
authors: Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire 03755, United StatescGeisel School of Medicine at Dartmouth, Department of Surgery, Hanover, New Hampshire 03755, United States.
authors: Kimberley S
authors: KS
authors: Samkoe
authors: Dartmouth College, Department of Physics & Astronomy, Hanover, New Hampshire 03755, United StatesbDartmouth College, Thayer School of Engineering, Hanover, New Hampshire 03755, United StatescGeisel School of Medicine at Dartmouth, Department of Surgery, H.
authors: Brian W
authors: BW
authors: Pogue
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism*; D005910:Glioma / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D006257:Head / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism*; D041622:Tomography, Optical / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes; D011993:Recombinant Fusion Proteins; D066246:ErbB Receptors
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