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Open Access 01-08-2019 | Research Article

Pharmacokinetic Modeling of Targeted Ultrasound Contrast Agents for Quantitative Assessment of Anti-Angiogenic Therapy: a Longitudinal Case-Control Study in Colon Cancer

Authors: Simona Turco, Ahmed El Kaffas, Jianhua Zhou, Amelie M. Lutz, Hessel Wijkstra, Jürgen K. Willmann, Massimo Mischi

Published in: Molecular Imaging and Biology | Issue 4/2019

Abstract

Purpose

To evaluate quantitative and semi-quantitative ultrasound molecular imaging (USMI) for antiangiogenic therapy monitoring in human colon cancer xenografts in mice.

Procedures

Colon cancer was established in 17 mice by injection of LS174T (N_r = 9) or CT26 (N_n = 8) cancer cells to simulate clinical responders and non-responders, respectively. Antiangiogenic treatment (bevacizumab; N_rt = N_nt = 5) or control treatment (saline; N_rc = 4, N_nc = 3) was administered at days 0, 3, and 7. Three-dimensional USMI was performed by injection at days 0, 1, 3, 7, and 10 of microbubbles targeted to the vascular endothelial growth factor receptor 2 (VEGFR2). Microbubble binding rate (k_b), estimated by first-pass binding model fitting, and semi-quantitative parameters late enhancement (LE) and differential targeted enhancement (dTE) were compared at each day to evaluate their ability to assess and predict the response to therapy. Correlation analysis with the ex-vivo immunohistological quantification of VEGFR2 expression and the percentage blood vessel area was also performed.

Results

Significant changes in the USMI parameters during treatment were observed only in the responders treated with bevacizumab (p-value < 0.05). Prediction of the response to therapy as early as 1 day after treatment was achieved by the quantitative parameter k_b (p-value < 0.01), earlier than possible by tumor volume quantification. USMI parameters could significantly distinguish between clinical responders and non-responders (p-value << 0.01) and correlated well with the ex-vivo quantification of VEGFR2 expression and the percentage blood vessels area (p-value << 0.01).

Conclusion

USMI (semi)quantitative parameters provide earlier assessment of the response to therapy compared to tumor volume, permit early prediction of non-responders, and correlate well with ex-vivo angiogenesis biomarkers.

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Title: Pharmacokinetic Modeling of Targeted Ultrasound Contrast Agents for Quantitative Assessment of Anti-Angiogenic Therapy: a Longitudinal Case-Control Study in Colon Cancer
Authors: Simona Turco
Ahmed El Kaffas
Jianhua Zhou
Amelie M. Lutz
Hessel Wijkstra
Jürgen K. Willmann
Massimo Mischi
Publication date: 01-08-2019
Publisher: Springer International Publishing
Published in: Molecular Imaging and Biology / Issue 4/2019
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-018-1274-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Pharmacokinetic Modeling of Targeted Ultrasound Contrast Agents for Quantitative Assessment of Anti-Angiogenic Therapy: a Longitudinal Case-Control Study in Colon Cancer

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

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