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Radiolabelled FGF-2 for Imaging Activated Fibroblasts in the Tumor Micro-Environment

Articolo
Data di Pubblicazione:
2024
Abstract:
Tumor associated fibroblasts (TAFs) play a key role in tumor growth and metastatization. TAFs overexpress different biomarkers that are usually expressed at low levels in physiological conditions. Among them are the fibroblast growth factor receptors (FGFRs) that bind the fibroblast growth factors (FGFs). In particular, the overexpression of FGFR-2c in tumors has been associated with advanced clinical stages and increased metastatization. Here, we developed a non-invasive tool to evaluate, in vivo, the expression of FGFR-2c in metastatic cancer. This is based on 99mTc-labelled FGF-2. Methods: 99mTc-FGF-2 was tested in vitro and in vivo in mice bearing allografts of sarcoma cells. Images of 99mTc-FGF-2 were acquired using a new portable high-resolution ultra-sensitive gamma camera for small animal imaging. Results: FGF-2 was labeled with high specific activity but low labelling efficiency, thus requiring post-labeling purification by gel-filtration chromatography. In vitro binding to 2C human keratinocytes showed a Kd of 3.36 × 10−9 M. In mice bearing J774A.1 cell allografts, we observed high and rapid tumor uptake of 99mTc-FGF-2 with a high Tumor/Blood ratio at 24 h post-injection (26.1 %ID/g and 12.9 %ID) with low kidney activity and moderate liver activity. Conclusions: we labeled FGF-2 with 99mTc and showed nanomolar Kd in vitro with human keratinocytes expressing FGF-2 receptors. In mice, 99mTc-FGF-2 rapidly and efficiently accumulated in tumors expressing FGF-2 receptors. This new radiopharmaceutical could be used in humans to image TAFs.
Tipologia CRIS:
1.1 Articolo in rivista
Keywords:
cancer imaging; fibroblasts; nuclear medicine; tumor microenvironment
Elenco autori:
Bentivoglio, V.; Galli, F.; Varani, M.; Ranieri, D.; Nayak, P.; D'Elia, A.; Soluri, A.; Massari, R.; Lauri, C.; Signore, A.
Autori di Ateneo:
RANIERI DANILO
Link alla scheda completa:
https://iris.unilink.it/handle/20.500.14085/21602
Pubblicato in:
BIOMOLECULES
Journal
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