PMID- 19735869 OWN - NLM STAT- MEDLINE DCOM- 20090921 LR - 20151119 IS - 1879-355X (Electronic) IS - 0360-3016 (Linking) VI - 75 IP - 2 DP - 2009 Oct 1 TI - Usefulness of HIF-1 imaging for determining optimal timing of combining bevacizumab and radiotherapy. PG - 463-7 LID - 10.1016/j.ijrobp.2009.02.083 [doi] AB - PURPOSE: To study the relationship between the hypoxia-inducible factor-1 (HIF-1) activity level after bevacizumab treatment and the antitumor effects of radiation to determine the optimal combination schedule of bevacizumab with radiotherapy. METHODS AND MATERIALS: The tumor hypoxia changes induced after bevacizumab treatment were evaluated using optical imaging with a HIF-1-dependent reporter gene using the NCI-H441 human lung adenocarcinoma xenograft model. The combined effects of bevacizumab with radiation were evaluated according to the timing of combination. RESULTS: In vivo imaging experiments revealed that bevacizumab treatment had little effect on intratumoral HIF-1 activity 1 day after bevacizumab treatment, but it dramatically upregulated it thereafter through increases in the hypoxic fractions of the tumors. When bevacizumab treatment was combined with 14 Gy of radiation at 24 h or 72 h after bevacizumab treatment, the former combination delayed, but the latter combination accelerated, tumor growth compared with irradiation alone. CONCLUSION: These data suggest that an optimal window exists for combining bevacizumab with radiotherapy that determines whether the combination will be beneficial and that the imaging of HIF-1 activity would be useful in determining this window. FAU - Ou, Guangfei AU - Ou G AD - Department of Radiation Oncology, Cancer Hospital Institute, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China. FAU - Itasaka, Satoshi AU - Itasaka S FAU - Zeng, Lihua AU - Zeng L FAU - Shibuya, Keiko AU - Shibuya K FAU - Yi, Junlin AU - Yi J FAU - Harada, Hiroshi AU - Harada H FAU - Hiraoka, Masahiro AU - Hiraoka M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Int J Radiat Oncol Biol Phys JT - International journal of radiation oncology, biology, physics JID - 7603616 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Biomarkers) RN - 0 (Hypoxia-Inducible Factor 1) RN - 2S9ZZM9Q9V (Bevacizumab) SB - IM MH - *Adenocarcinoma/blood supply/drug therapy/metabolism/radiotherapy MH - Angiogenesis Inhibitors/*administration & dosage MH - Animals MH - Antibodies, Monoclonal/*administration & dosage MH - Antibodies, Monoclonal, Humanized MH - Bevacizumab MH - Biomarkers/metabolism MH - *Cell Hypoxia/drug effects MH - Cell Line, Tumor MH - Combined Modality Therapy/methods MH - Genes, Reporter MH - Humans MH - Hypoxia-Inducible Factor 1/genetics/*metabolism MH - In Situ Nick-End Labeling MH - *Lung Neoplasms/blood supply/drug therapy/metabolism/radiotherapy MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Random Allocation MH - Time Factors MH - Xenograft Model Antitumor Assays EDAT- 2009/09/09 06:00 MHDA- 2009/09/22 06:00 CRDT- 2009/09/09 06:00 PHST- 2008/09/21 00:00 [received] PHST- 2009/02/04 00:00 [revised] PHST- 2009/02/04 00:00 [accepted] PHST- 2009/09/09 06:00 [entrez] PHST- 2009/09/09 06:00 [pubmed] PHST- 2009/09/22 06:00 [medline] AID - S0360-3016(09)00847-5 [pii] AID - 10.1016/j.ijrobp.2009.02.083 [doi] PST - ppublish SO - Int J Radiat Oncol Biol Phys. 2009 Oct 1;75(2):463-7. doi: 10.1016/j.ijrobp.2009.02.083.