Radiolabelled FGF-2 for Imaging Activated Fibroblasts in the Tumor Micro-Environment
Valeria Bentivoglio,
Filippo Galli,
Michela Varani,
Danilo Ranieri,
Pallavi Nayak,
Annunziata D’Elia,
Andrea Soluri,
Roberto Massari,
Chiara Lauri,
Alberto Signore
Affiliations
Valeria Bentivoglio
Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of Rome, 00189 Rome, Italy
Filippo Galli
Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of Rome, 00189 Rome, Italy
Michela Varani
Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of Rome, 00189 Rome, Italy
Danilo Ranieri
Department of Life Sciences, Health and Healthcare Professions, University “Link Campus University”, 00189 Rome, Italy
Pallavi Nayak
Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of Rome, 00189 Rome, Italy
Annunziata D’Elia
Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), 00015 Monterotondo Scalo, Italy
Andrea Soluri
Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), 00015 Monterotondo Scalo, Italy
Roberto Massari
Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), 00015 Monterotondo Scalo, Italy
Chiara Lauri
Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of Rome, 00189 Rome, Italy
Alberto Signore
Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of Rome, 00189 Rome, Italy
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.
