title: Monitoring the effects of anti-angiogenesis on the radiation sensitivity of pancreatic cancer xenografts using dynamic contrast-enhanced computed tomography.
abstract: OBJECTIVE
  To image the intratumor vascular physiological status of pancreatic tumors xenografts and their response to anti-angiogenic therapy using dynamic contrast-enhanced computed tomography (DCE-CT), and to identify parameters of vascular physiology associated with tumor x-ray sensitivity after anti-angiogenic therapy.
  
  
  METHODS
  Nude mice bearing human BxPC-3 pancreatic tumor xenografts were treated with 5 Gy of radiation therapy (RT), either a low dose (40 mg/kg) or a high dose (150 mg/kg) of DC101, the anti-VEGF receptor-2 anti-angiogenesis antibody, or with combination of low or high dose DC101 and 5 Gy RT (DC101-plus-RT). DCE-CT scans were longitudinally acquired over a 3-week period post-DC101 treatment. Parametric maps of tumor perfusion and fractional plasma volume (Fp) were calculated and their averaged values and histogram distributions evaluated and compared to controls, from which a more homogeneous physiological window was observed 1-week post-DC101. Mice receiving a combination of DC101-plus-RT(5 Gy) were imaged baseline before receiving DC101 and 1 week after DC101 (before RT). Changes in perfusion and Fp were compared with alternation in tumor growth delay for RT and DC101-plus-RT (5 Gy)-treated tumors.
  
  
  RESULTS
  Pretreatment with low or high doses of DC101 before RT significantly delayed tumor growth by an average 7.9 days compared to RT alone (P ≤ .01). The increase in tumor growth delay for the DC101-plus-RT-treated tumors was strongly associated with changes in tumor perfusion (ΔP>-15%) compared to RT treated tumors alone (P=.01). In addition, further analysis revealed a trend linking the tumor's increased growth delay to its tumor volume-to-DC101 dose ratio.
  
  
  CONCLUSIONS
  DCE-CT is capable of monitoring changes in intratumor physiological parameter of tumor perfusion in response to anti-angiogenic therapy of a pancreatic human tumor xenograft that was associated with enhanced radiation response.
authors.affiliation: School of Health Sciences, Purdue University, West Lafayette, Indiana; Radiation Oncology, University of Washington, Seattle, Washington.
authors.forename: Ning
authors.initials: N
authors.lastname: Cao
authors.affiliation: Radiation Oncology, University of California-Los Angeles, Los Angeles, California.
authors.forename: Minsong
authors.initials: M
authors.lastname: Cao
authors.affiliation: Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Helen
authors.initials: H
authors.lastname: Chin-Sinex
authors.affiliation: Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Marc
authors.initials: M
authors.lastname: Mendonca
authors.affiliation: Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Song-Chu
authors.initials: SC
authors.lastname: Ko
authors.affiliation: School of Health Sciences, Purdue University, West Lafayette, Indiana; Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: kstantz@purdue.edu.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Stantz
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D049109:Cell Proliferation; D003131:Combined Modality Therapy / Q000379:methods; D003287:Contrast Media; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D011836:Radiation Tolerance / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D003287:Contrast Media; C511761:DC101 monoclonal antibody