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

F. Galli, M. Artico, S. Taurone, I. Manni, E. Bianchi, G. Piaggio, B. D. Weintraub, M. W. Szkudlinski, E. Agostinelli, R. A. J. O. Dierckx, A. Signore

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)2171-2179
Number of pages9
JournalInternational Journal of Oncology
Volume50
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

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Vascular Endothelial Growth Factor A
Tumor Microenvironment
Neoplasms
Cellular Microenvironment
Vascular Endothelial Growth Factor Receptor
Angiogenesis Inhibitors
Human Umbilical Vein Endothelial Cells
Cellular Structures
Heterografts
Radionuclide Imaging
Endothelial Cells
Growth

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Radiolabeling of VEGF165 with 99mTc to evaluate VEGFR expression in tumor angiogenesis. / Galli, F.; Artico, M.; Taurone, S.; Manni, I.; Bianchi, E.; Piaggio, G.; Weintraub, B. D.; Szkudlinski, M. W.; Agostinelli, E.; Dierckx, R. A. J. O.; Signore, A.

In: International Journal of Oncology, Vol. 50, No. 6, 01.06.2017, p. 2171-2179.

Research output: Contribution to journalArticle

Galli, F, Artico, M, Taurone, S, Manni, I, Bianchi, E, Piaggio, G, Weintraub, BD, Szkudlinski, MW, Agostinelli, E, Dierckx, RAJO & Signore, A 2017, 'Radiolabeling of VEGF165 with 99mTc to evaluate VEGFR expression in tumor angiogenesis', International Journal of Oncology, vol. 50, no. 6, pp. 2171-2179. https://doi.org/10.3892/ijo.2017.3989 [doi]
Galli, F. ; Artico, M. ; Taurone, S. ; Manni, I. ; Bianchi, E. ; Piaggio, G. ; Weintraub, B. D. ; Szkudlinski, M. W. ; Agostinelli, E. ; Dierckx, R. A. J. O. ; Signore, A. / Radiolabeling of VEGF165 with 99mTc to evaluate VEGFR expression in tumor angiogenesis. In: International Journal of Oncology. 2017 ; Vol. 50, No. 6. pp. 2171-2179.
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