title: Use of the ODD-luciferase transgene for the non-invasive imaging of spontaneous tumors in mice.
abstract: BACKGROUND
  In humans, imaging of tumors provides rapid, accurate assessment of tumor growth and location. In laboratory animals, however, the imaging of spontaneously occurring tumors continues to pose many technical and logistical problems. Recently a mouse model was generated in which a chimeric protein consisting of HIF-1α oxygen-dependent degradation domain (ODD) fused to luciferase was ubiquitously expressed in all tissues. Hypoxic stress leads to the accumulation of ODD-luciferase in the tissues of this mouse model which can be identified by non-invasive bioluminescence measurement. Since solid tumors often contain hypoxic regions, we performed proof-of-principle experiments testing whether this transgenic mouse model may be used as a universal platform for non-invasive imaging analysis of spontaneous solid tumors.
  
  
  METHODS
  ODD-luciferase transgenic mice were bred with MMTV-neu/beclin1+/- mice. Upon injection of luciferin, bioluminescent background of normal tissues in the transgenic mice and bioluminescent signals from spontaneously mammary carcinomas were measured non-invasively with an IVIS Spectrum imaging station. Tumor volumes were measured manually and the histology of tumor tissues was analyzed.
  
  
  CONCLUSIONS
  Our results show that spontaneous mammary tumors in ODD-luciferase transgenic mice generate substantial bioluminescent signals, which are clearly discernable from background tissue luminescence. Moreover, we demonstrate a strong quantitative correlation between the bioluminescent tumor contour and the volume of palpable tumors. We further demonstrate that shrinkage of the volume of spontaneous tumors in response to chemotherapeutic treatment can be determined quantitatively using this system. Finally, we show that the growth and development of spontaneous tumors can be monitored longitudinally over several weeks. Thus, our results suggest that this model could potentially provide a practical, reliable, and cost-effective non-invasive quantitative method for imaging spontaneous solid tumors in mice.
authors.affiliation: Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey, United States of America.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Goldman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Chen
authors.forename: Robert
authors.initials: R
authors.lastname: Taylor
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Whitney
authors.initials: W
authors.lastname: Petrosky
authors.forename: Michael
authors.initials: M
authors.lastname: Reiss
authors.forename: Shengkan
authors.initials: S
authors.lastname: Jin
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000071186:Beclin-1; D015687:Cell Hypoxia; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry*; D008156:Luciferases / Q000235:genetics*; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D008324:Mammary Tumor Virus, Mouse / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000473:pathology; D017434:Protein Structure, Tertiary; D012074:Remission Induction; D019076:Transgenes / Q000235:genetics*; D047368:Tumor Burden
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008156:Luciferases