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.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.