Abstract
Angiogenesis is a critical step in tumor development, in which vascular endothelial growth factor (VEGF) is a key growth aspect. Heat shock protein 90 (HSP90), a molecular chaperone, is essential for the activity of key proteins involved in VEGF transcription. Currently, no biomarkers to predict the effect of, or monitor, HSP90 inhibition therapy in individual patients exist. (89)Zr-bevacizumab PET provides a noninvasive tool to monitor tumor VEGF levels. The aim of this study was to investigate (89)Zr-bevacizumab PET for early antiangiogenic tumor response evaluation of treatment with the new HSP90 inhibitor NVP-AUY922. In xenografts of A2780 and its cisplatin-resistant CP70 human ovarian cancer subline, (89)Zr-bevacizumab small-animal PET was performed before and after NVP-AUY922 treatment and verified with histologic response and ex vivo tumor VEGF levels. Compared with pretreatment values, 2 wk of NVP-AUY922 treatment decreased (89)Zr-bevacizumab uptake by 44.4% (P = 0.0003) in A2780 xenografts, whereas tumor uptake was not affected in CP70 xenografts. The same pattern was observed in A2780 and CP70 tumor VEGF levels, measured with enzyme-linked immunosorbent assay, and mean vessel density after NVP-AUY922 treatment. These findings coincided with reduction in the proliferation rate, assessed by Ki67 staining, in A2780 tumor tissue only. CONCLUSION: (89)Zr-bevacizumab PET was in line with the antiangiogenic response and direct antitumor effects after NVP-AUY922 treatment, supporting the specificity of (89)Zr-bevacizumab PET as a sensitive technique to monitor the antiangiogenic response of HSP90 inhibition in vivo.
| Original language | English |
|---|---|
| Pages (from-to) | 761-767 |
| Number of pages | 7 |
| Journal | Journal of Nuclear Medicine |
| Volume | 51 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 1 May 2010 |
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89Zr-bevacizumab PET of early antiangiogenic tumor response to treatment with HSP90 inhibitor NVP-AUY922. / Nagengast, Wouter B.; de Korte, Maarten A.; Oude Munnink, Thijs H.; Timmer-Bosscha, Hetty; den Dunnen, Wifred F.; Hollema, Harry; de Jong, Johan R.; Jensen, Michael R.; Quadt, Cornelia; Garcia-Echeverria, Carlos; van Dongen, Guus A.M.S.; Lub-de Hooge, Marjolijn N.; Schröder, Carolien P.; de Vries, Elisabeth G.E.
In: Journal of Nuclear Medicine, Vol. 51, No. 5, 01.05.2010, p. 761-767.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - 89Zr-bevacizumab PET of early antiangiogenic tumor response to treatment with HSP90 inhibitor NVP-AUY922.
AU - Nagengast, Wouter B.
AU - de Korte, Maarten A.
AU - Oude Munnink, Thijs H.
AU - Timmer-Bosscha, Hetty
AU - den Dunnen, Wifred F.
AU - Hollema, Harry
AU - de Jong, Johan R.
AU - Jensen, Michael R.
AU - Quadt, Cornelia
AU - Garcia-Echeverria, Carlos
AU - van Dongen, Guus A.M.S.
AU - Lub-de Hooge, Marjolijn N.
AU - Schröder, Carolien P.
AU - de Vries, Elisabeth G.E.
PY - 2010/5/1
Y1 - 2010/5/1
N2 - Angiogenesis is a critical step in tumor development, in which vascular endothelial growth factor (VEGF) is a key growth aspect. Heat shock protein 90 (HSP90), a molecular chaperone, is essential for the activity of key proteins involved in VEGF transcription. Currently, no biomarkers to predict the effect of, or monitor, HSP90 inhibition therapy in individual patients exist. (89)Zr-bevacizumab PET provides a noninvasive tool to monitor tumor VEGF levels. The aim of this study was to investigate (89)Zr-bevacizumab PET for early antiangiogenic tumor response evaluation of treatment with the new HSP90 inhibitor NVP-AUY922. In xenografts of A2780 and its cisplatin-resistant CP70 human ovarian cancer subline, (89)Zr-bevacizumab small-animal PET was performed before and after NVP-AUY922 treatment and verified with histologic response and ex vivo tumor VEGF levels. Compared with pretreatment values, 2 wk of NVP-AUY922 treatment decreased (89)Zr-bevacizumab uptake by 44.4% (P = 0.0003) in A2780 xenografts, whereas tumor uptake was not affected in CP70 xenografts. The same pattern was observed in A2780 and CP70 tumor VEGF levels, measured with enzyme-linked immunosorbent assay, and mean vessel density after NVP-AUY922 treatment. These findings coincided with reduction in the proliferation rate, assessed by Ki67 staining, in A2780 tumor tissue only. CONCLUSION: (89)Zr-bevacizumab PET was in line with the antiangiogenic response and direct antitumor effects after NVP-AUY922 treatment, supporting the specificity of (89)Zr-bevacizumab PET as a sensitive technique to monitor the antiangiogenic response of HSP90 inhibition in vivo.
AB - Angiogenesis is a critical step in tumor development, in which vascular endothelial growth factor (VEGF) is a key growth aspect. Heat shock protein 90 (HSP90), a molecular chaperone, is essential for the activity of key proteins involved in VEGF transcription. Currently, no biomarkers to predict the effect of, or monitor, HSP90 inhibition therapy in individual patients exist. (89)Zr-bevacizumab PET provides a noninvasive tool to monitor tumor VEGF levels. The aim of this study was to investigate (89)Zr-bevacizumab PET for early antiangiogenic tumor response evaluation of treatment with the new HSP90 inhibitor NVP-AUY922. In xenografts of A2780 and its cisplatin-resistant CP70 human ovarian cancer subline, (89)Zr-bevacizumab small-animal PET was performed before and after NVP-AUY922 treatment and verified with histologic response and ex vivo tumor VEGF levels. Compared with pretreatment values, 2 wk of NVP-AUY922 treatment decreased (89)Zr-bevacizumab uptake by 44.4% (P = 0.0003) in A2780 xenografts, whereas tumor uptake was not affected in CP70 xenografts. The same pattern was observed in A2780 and CP70 tumor VEGF levels, measured with enzyme-linked immunosorbent assay, and mean vessel density after NVP-AUY922 treatment. These findings coincided with reduction in the proliferation rate, assessed by Ki67 staining, in A2780 tumor tissue only. CONCLUSION: (89)Zr-bevacizumab PET was in line with the antiangiogenic response and direct antitumor effects after NVP-AUY922 treatment, supporting the specificity of (89)Zr-bevacizumab PET as a sensitive technique to monitor the antiangiogenic response of HSP90 inhibition in vivo.
UR - http://www.scopus.com/inward/record.url?scp=77952302437&partnerID=8YFLogxK
U2 - 10.2967/jnumed.109.071043
DO - 10.2967/jnumed.109.071043
M3 - Article
VL - 51
SP - 761
EP - 767
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
SN - 0161-5505
IS - 5
ER -