title: Dynamic dual-tracer MRI-guided fluorescence tomography to quantify receptor density in vivo.
abstract: The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent tracers injected simultaneously, one tracer targeted to the receptor of interest and the other tracer a nontargeted reference. These dynamic tracer data were then fit to a dual-tracer compartmental model to estimate the density of receptors available for binding in the tissue. Applying this approach to mice with deep-seated gliomas that overexpress the EGF receptor produced an estimate of available receptor density of 2.3 ± 0.5 nM (n = 5), consistent with values estimated in comparative invasive imaging and ex vivo studies.
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA. scott.c.davis@dartmouth.edu
authors.forename: Scott C
authors.initials: SC
authors.lastname: Davis
authors.forename: Kimberley S
authors.initials: KS
authors.lastname: Samkoe
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Tichauer
authors.forename: Kristian J
authors.initials: KJ
authors.lastname: Sexton
authors.forename: Jason R
authors.initials: JR
authors.lastname: Gunn
authors.forename: Sophie J
authors.initials: SJ
authors.lastname: Deharvengt
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pogue
mesh_terms: D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism; D005453:Fluorescence; D005910:Glioma / Q000378:metabolism*; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D041622:Tomography, Optical / Q000379:methods*
chemical_list: D011956:Receptors, Cell Surface; D066246:ErbB Receptors
keywords: engineered proteins; molecular imaging; oncology; optical imaging; spectroscopy