title: Bioluminescence imaging correlates with tumor serum marker, organ weights, histology, and human DNA levels during treatment of orthotopic tumor xenografts with antibodies.
abstract: OBJECTIVE
  In this study, we correlate results of bioluminescence measurements with established readouts for assessing therapeutic efficacy of antibodies in orthotopic cancer xenografts.
  
  
  METHODS
  An orthotopic tumor model of pancreatic cancer (AsPC-1-luc) and experimental lung metastasis (A549-luc) were established. Whole-body bioluminescence imaging (BLI) was performed to observe tumor progression under therapy with antibodies targeting different receptor kinases (primary readout). For purpose of verification, anti-tumoral efficacy was cross-validated with results obtained by measurement of organ weights, histology, tumor serum marker analysis (CYFRA 21-1), and quantification of human DNA concentration in the organ of interest (secondary readouts).
  
  
  RESULTS
  Anti-tumoral efficacy is demonstrated for the antibodies tested. In the pancreas xenograft, a tumor growth inhibition of 95% (p < 0.01) was achieved as compared to control. Therapeutic efficacy could be identified as soon as 1 week after initiation of treatment. In the model of experimental lung metastasis, antibody treatment significantly suppressed tumor growth up to 75% (p < 0.05). All imaging results were confirmed by correlation analysis showing excellent agreement with the secondary readouts.
  
  
  CONCLUSIONS
  BLI was demonstrated to be a reliable tool for monitoring early drug responses in orthotopic small animal cancer models. BLI allows rapid and non-invasive assessment of tumor load in the animal over time and, thus, provides a suitable method for routine use in preclinical cancer research.
authors.affiliation: Roche Diagnostics GmbH, pRED, Pharma Research & Early Development, DTA Oncology, Nonnenwald 2, 82377 Penzberg, Germany. thomas.poeschinger@roche.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Poeschinger
authors.forename: Anja
authors.initials: A
authors.lastname: Renner
authors.forename: Thomas
authors.initials: T
authors.lastname: Weber
authors.forename: Werner
authors.initials: W
authors.lastname: Scheuer
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008163:Luminescent Measurements / Q000379:methods*; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D051379:Mice; D008812:Mice, Hairless; D016513:Mice, SCID; D057054:Molecular Imaging / Q000379:methods; D000069444:Omalizumab; D009929:Organ Size / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015203:Reproducibility of Results; D023041:Xenograft Model Antitumor Assays
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D000069444:Omalizumab