title: Radiolabeled111In-FGF-2 Is Suitable for In Vitro/Ex Vivo Evaluations and In Vivo Imaging.
abstract: Fibroblast growth factor-2 (FGF-2) is a potent modulator of cell growth and regulation, with improper FGF-2 signaling being involved in impaired responses to injury or even cancer. Therefore, the exploitation of FGF-2 as a therapeutic drives the prerequisite for effective insight into drug disposition kinetics. In this article, we present an111In-radiolabeled FGF-2 derivative for noninvasive imaging in small animals deploying single photon emission tomography (SPECT).111In-FGF-2 is equally well suitable for in vitro and ex vivo investigations as125I-FGF-2. Furthermore,111In-FGF-2 permits the performance of in vivo imaging, for example for the analysis of FGF-2 containing pharmaceutical formulations in developmental or preclinical stages.111In-FGF-2 had affinity for the low-molecular-weight heparin enoxaparin identical to that of unlabeled FGF-2 (Kd: 0.6 ± 0.07 μM and 0.33 ± 0.03 μM, respectively) as assessed by isothermal titration calorimetry. The binding of111In-FGF-2 to heparan sulfate proteoglycans (HPSGs) and the biological activity were comparable to those of unlabeled FGF-2, with EC50values of 12 ± 2 pM and 25 ± 6 pM, respectively. In vivo biodistribution in healthy nude mice indicated a predominant accumulation of111In-FGF-2 in filtering organs and minor uptake in the retina and the salivary and pituitary glands, which was confirmed by SPECT imaging. Therefore,111In-FGF-2 is a valid tracer for future noninvasive animal imaging of FGF-2 in pharmaceutical development.
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute , 5232 Villigen PSI, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Moscaroli
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wurzburg , 97074 Wurzburg, Germany.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Jones
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wurzburg , 97074 Wurzburg, Germany.
authors.forename: Tessa
authors.initials: T
authors.lastname: Lühmann
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wurzburg , 97074 Wurzburg, Germany.
authors.forename: Lorenz
authors.identifier: 0000-0002-7549-7627
authors.initials: L
authors.lastname: Meinel
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich , 8092 Zurich, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wälti
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute , 5232 Villigen PSI, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Blanc
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute , 5232 Villigen PSI, Switzerland.
authors.forename: Eliane
authors.initials: E
authors.lastname: Fischer
authors.affiliation: Laboratory of Biomolecular Research, Department of Biology and Chemistry, Paul Scherrer Institute , 5232 Villigen PSI, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Hilbert
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute , 5232 Villigen PSI, Switzerland.|Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich , 8092 Zurich, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute , 5232 Villigen PSI, Switzerland.
authors.forename: Martin
authors.identifier: 0000-0002-1110-2665
authors.initials: M
authors.lastname: Béhé
mesh_terms: D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000378:metabolism; D006801:Humans; D007205:Indium Radioisotopes / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D011485:Protein Binding / Q000502:physiology; D014018:Tissue Distribution / Q000502:physiology; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D019812:Heparan Sulfate Proteoglycans; D006495:Heparin, Low-Molecular-Weight; D007205:Indium Radioisotopes; D016222:Fibroblast Growth Factor 2
keywords: fibroblast growth factor-2 (FGF-2); in vivo imaging; residue-specific radiolabeling; single photon emission tomography (SPECT)