Imaging biomarkers to monitor response to the hypoxia-activated prodrug TH-302 in the MiaPaCa2 flank xenograft model.

Magnetic Resonance Imaging
Julio Cárdenas-RodríguezAmanda F Baker

Abstract

TH-302, a hypoxia-activated anticancer prodrug, was evaluated for antitumor activity and changes in dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) in a mouse model of pancreatic cancer. TH-302 monotherapy resulted in a significant delay in tumor growth compared to vehicle-treated controls. TH-302 treatment was also associated with a significant decrease in the volume transfer constant (K(trans)) compared to vehicle-treated controls 1 day following the first dose measured using DCE-MRI. This early decrease in K(trans) following the first dose as measured is consistent with selective killing of the hypoxic fraction of cells which are associated with enhanced expression of hypoxia inducible transcription factor-1 alpha that regulates expression of permeability and perfusion factors including vascular endothelial growth factor-A. No changes were observed in DW-MRI following treatment with TH-302, which may indicate that this technique is not sensitive enough to detect changes in small hypoxic fractions of the tumor targeted by TH-302. These results suggest that changes in tumor permeability and/or perfusion may be an early imaging biomarker for response to TH-302 therapy.

References

Jul 10, 1999·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·T P TrouardA F Gmitro
Aug 10, 2000·Neoplasia : an International Journal for Oncology Research·J L EvelhochH M Swartz
Jun 22, 2005·Neoplasia : an International Journal for Oncology Research·Bénédicte F JordanRobert J Gillies
Feb 9, 2008·Journal of Medicinal Chemistry·Jian-Xin DuanMark Matteucci
Mar 13, 2010·Future Oncology·William A Denny
Feb 18, 2011·Angiogenesis·C E EvansA Smith
Feb 18, 2011·Journal of Cellular Biochemistry·Jessica Cassavaugh, Karen M Lounsbury
Mar 19, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Glen J WeissHoward A Burris

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Citations

Dec 12, 2012·Magnetic Resonance Imaging·Julio Cárdenas-RodríguezMark D Pagel
Sep 2, 2015·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Ludwig J DuboisPhilippe Lambin
Feb 24, 2015·Seminars in Nuclear Medicine·Joseph G Rajendran, Kenneth A Krohn
Jul 1, 2017·Acta Oncologica·Catherine S WegnerEinar K Rofstad
Sep 30, 2016·Anti-cancer Drugs·Hani M BabikerMitesh J Borad
Jul 26, 2017·Antioxidants & Redox Signaling·Yoichi TakakusagiMurali C Krishna
Oct 3, 2018·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Joshua M GoldenbergMark D Pagel
Feb 1, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Natalia Baran, Marina Konopleva
Jun 13, 2019·Cancer Research·Bruna V Jardim-PerassiGary V Martinez

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