title: Tailoring Fluorescent Dyes To Optimize a Hybrid RGD-Tracer.
abstract: Quantitative assessment of affinity and kinetics is a critical component in the development of (receptor-targeted) radiotracers. For fluorescent tracers, such an assessment is currently not yet applied, while (small) changes in chemical composition of the fluorescent component might have substantial influence on the overall properties of a fluorescent tracer. Hybrid imaging labels that contain both a radiolabel and a fluorescent dye can be used to evaluate both the affinity (fluorescent label) and the in vivo distribution (radiolabel) of a targeted tracer. We present a hybrid label oriented and matrix-based scoring approach that enabled quantitative assessment of the influence of (overall) charge and lipophilicity of the fluorescent label on the (in vivo) characteristics of αvβ3-integrin targeted tracers. Systematic chemical alterations in the fluorescent dye were shown to result in a clear difference in the in vivo distribution of the different hybrid tracers. The applied evaluation technique resulted in an optimized targeted tracer for αvβ3-integrin, which combined the highest T/M ratio with the lowest uptake in other organs. Obviously this selection concept would also be applicable during the development of other (receptor-targeted) imaging tracers.
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center , Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Anton
authors.initials: A
authors.lastname: Bunschoten
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center , Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Danny M
authors.initials: DM
authors.lastname: van Willigen
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center , Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Tessa
authors.initials: T
authors.lastname: Buckle
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center , Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.|Departments of Urology and Head and Neck Surgery & Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital , Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Nynke S
authors.initials: NS
authors.lastname: van den Berg
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center , Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Mick M
authors.initials: MM
authors.lastname: Welling
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center , Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Silvia J
authors.initials: SJ
authors.lastname: Spa
authors.affiliation: Pharmaceutical Radiochemistry, Faculties of Chemistry and Medicine, Technische Universität München , 85748 Garching, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center , Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.|Departments of Urology and Head and Neck Surgery & Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital , Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Fijs W B
authors.initials: FW
authors.lastname: van Leeuwen
mesh_terms: D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007553:Isotope Labeling; D064847:Multimodal Imaging / Q000379:methods*; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D061848:Optical Imaging; D011849:Radioactive Tracers; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D005456:Fluorescent Dyes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D011849:Radioactive Tracers; C047981:arginyl-glycyl-aspartic acid