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European Journal of Nuclear Medicine and Molecular Imaging

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01-07-2011 | Original Article

PET imaging of early response to the tyrosine kinase inhibitor ZD4190

Authors: Min Yang, Haokao Gao, Yongjun Yan, Xilin Sun, Kai Chen, Qimeng Quan, Lixin Lang, Dale Kiesewetter, Gang Niu, Xiaoyuan Chen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 7/2011

Abstract

Purpose

We evaluated noninvasive positron emission tomography (PET) imaging for monitoring tumor response to the VEGFR-2 tyrosine kinase (TK) inhibitor ZD4190 during cancer therapy.

Experimental design

Orthotopic MDA-MB-435 tumor-bearing mice were treated with ZD4190 (100 mg/kg orally per day for three consecutive days). Tumor growth was monitored by caliper measurement. During the therapeutic period, longitudinal PET scans were acquired using ¹⁸F-FDG, ¹⁸F-FLT and ¹⁸F-FPPRGD2 as imaging tracers to evaluate tumor glucose metabolism, tumor cell proliferation, and angiogenesis, respectively. Imaging metrics were validated by immunohistochemical analysis of Ki67, GLUT-1, F4/80, CD31, murine integrin β3, and human integrin αvβ3.

Results

Three consecutive daily oral administrations of 100 mg/kg of ZD4190 were effective in delaying MDA-MB-435 tumor growth. A significant difference in tumor volume was observed on day 7 between the treatment group and the control group (p < 0.01). After the final treatment, tumor growth resumed after a short delay. In the control tumors, ¹⁸F-FPPRGD2 uptake was stable between days 0 and 7. In ZD4190-treated tumors, ¹⁸F-FPPRGD2 uptake had decreased significantly relative to baseline by 26.74±8.12% (p < 0.05) on day 1 and by 41.19±6.63% (p < 0.01) on day 3, then had returned to baseline on day 7. Tumor uptake of ¹⁸F-FLT had also decreased on both day 1 and day 3 after initiation of ZD4190 treatment. No significant change in ¹⁸F-FDG uptake in ZD4190-treated tumors was observed, however, compared with the control group. All of the imaging findings were supported by ex vivo analysis of related biomarkers.

Conclusion

The longitudinal imaging results demonstrated the usefulness of quantitative ¹⁸F-FLT and ¹⁸F-FPPRGD2 PET imaging in evaluating the early antiproliferative and antiangiogenic effects of ZD4190. The quantification data from the PET imaging were consistent with the pattern of initial growth inhibition with treatment, followed by tumor relapse after treatment cessation.

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Title: PET imaging of early response to the tyrosine kinase inhibitor ZD4190
Authors: Min Yang
Haokao Gao
Yongjun Yan
Xilin Sun
Kai Chen
Qimeng Quan
Lixin Lang
Dale Kiesewetter
Gang Niu
Xiaoyuan Chen
Publication date: 01-07-2011
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 7/2011
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-011-1742-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

PET imaging of early response to the tyrosine kinase inhibitor ZD4190

Abstract

Purpose

Experimental design

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Experimental design

Results

Conclusion

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