Moscaroli, Alessandra and Behe, Martin (2017) Radiolabeling and Characterization of 111In-FGF-2 for In Vivo Imaging. Mol Pharm. 2017 Mar 6;14(3):639-648. doi: 10.1021/acs.molpharmaceut.6b00913..

Abstract

Fibroblast growth factor-2 (FGF-2) is a regeneration potent modulator of cell growth and regulation, with improper FGF2-signaling being involved in impaired responses to injury or even cancer. Therefore, the exploitation of FGF2 as a therapeutic drives the prerequisite for effective insight into drug disposition kinetics. In this article, we present an 111In-radiolabeled FGF-2 derivative for non-invasive imaging in small animals deploying Single Photon Emission Tomography (SPECT). 111In-FGF-2 is equally well suitable for in vitro and ex vivo investigations as 125I-FGF-2. Furthermore, 111In-FGF-2 permits to perform in vivo imaging, for example for the analysis of FGF-2 containing pharmaceutical formulations in developmental or pre-clinical stages. Radiolabeled FGF-2 had the same affinity for the low molecular weight heparin enoxaparin (Kd: 0.6 ± 0.07 µM resp. 0.33 ± 0.03 µM) and heparan sulfate proteoglycan (HPSG) binding as assessed by a saturation binding assay (Kd value in the nanomolar range of 104 ± 8 nM) as compared to natIn-FGF-2 and unlabeled FGF-2. FGF-2 and natIn-FGF-2 had similar proliferative effects on fibroblasts (EC50 = 12 ± 2 pM resp. 25 ± 6 pM). In vivo biodistribution in healthy nude mice indicated a predominant accumulation of 111In-FGF-2 in filtering organs and minor uptake in the retina, salivary, and pituitary glands, respectively, which was confirmed by SPECT imaging. Therefore, 111In-FGF-2 is a valid tracer for future non-invasive animal imaging of FGF-2 in pharmaceutical development.

Item Type:	Article
Date Deposited:	26 Apr 2017 00:45
Last Modified:	26 Apr 2017 00:45
URI:	https://oak.novartis.com/id/eprint/30747