Radiolabeling of VEGF165 with 99mTc to evaluate VEGFR expression in tumor angiogenesis

Galli,Filippo; Artico,Marco; Taurone,Samanta; Manni,Isabella; Bianchi,Enrica; Piaggio,Giulia; Weintraub,Bruce D.; Szkudlinski,Mariusz W.; Agostinelli,Enzo; Dierckx,Rudi A.J.O.; Signore,Alberto

doi:10.3892/ijo.2017.3989

Radiolabeling of VEGF165 with 99mTc to evaluate VEGFR expression in tumor angiogenesis

Authors:
- Filippo Galli
- Marco Artico
- Samanta Taurone
- Isabella Manni
- Enrica Bianchi
- Giulia Piaggio
- Bruce D. Weintraub
- Mariusz W. Szkudlinski
- Enzo Agostinelli
- Rudi A.J.O. Dierckx
- Alberto Signore
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Affiliations: Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, ‘Sapienza’ University of Rome, Rome, Italy, Department of Sensory Organs, ‘Sapienza’ University of Rome, Rome, Italy, SAFU UOSD, Department of Research, Advanced Diagnostics and Technological Innovation, Regina Elena National Cancer Institute, Rome, Italy, Trophogen Inc., Rockville, MD, USA, Department of Biochemical Sciences ‘A. Rossi Fanelli’, ‘Sapienza’ University of Rome, Rome, Italy, Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
Published online on: May 8, 2017 https://doi.org/10.3892/ijo.2017.3989
Pages: 2171-2179

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Abstract

Angiogenesis is the main process responsible for tumor growth and metastatization. The principal effector of such mechanism is the vascular endothelial growth factor (VEGF) secreted by cancer cells and other components of tumor microenvironment. Radiolabeled VEGF analogues may provide a useful tool to noninvasively image tumor lesions and evaluate the efficacy of anti-angiogenic drugs that block the VEGFR pathway. Aim of the present study was to radiolabel the human VEGF165 analogue with 99mTechnetium (99mTc) and to evaluate the expression of VEGFR in both cancer and endothelial cells in the tumor microenvironment. 99mTc-VEGF showed in vitro binding to HUVEC cells and in vivo to xenograft tumors in mice (ARO, K1 and HT29). By comparing in vivo data with immunohistochemical analysis of excised tumors we found an inverse correlation between 99mTc-VEGF165 uptake and VEGF histologically detected, but a positive correlation with VEGF receptor expression (VEGFR1). Results of our studies indicate that endogenous VEGF production by cancer cells and other cells of tumor microenvironment should be taken in consideration when performing scintigraphy with radiolabeled VEGF, because of possible false negative results due to saturation of VEGFRs.

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