title: Real-time whole-body imaging of an orthotopic metastatic prostate cancer model expressing red fluorescent protein.
abstract: BACKGROUND
  We describe here, a whole-body imageable spontaneous metastatic model of human prostate cancer developed by surgical orthotopic implantation (SOI) and visualized by red fluorescent protein (RFP) expression.
  
  
  METHODS
  Human prostate cancer PC-3 cells were transduced with the pLNCX2-DsRed-2-RFP retroviral vector containing the RFP and neomycin-resistance genes. A stable RFP-expressing PC-3 clone was selected in 800 microg/ml G418 in vitro and injected subcutaneously in nude mice. Stable high-level expression of RFP was maintained in the subcutaneously-growing tumors. To utilize RFP expression for metastasis studies, fragments of the subcutaneously-growing tumor, which were comprised of RFP-expressing cells, were implanted by SOI in the prostate of nude mice.
  
  
  RESULTS
  Primary tumor growth, progression, and subsequent lymphatic metastases were visualized in live, intact animals in real time by whole-body RFP fluorescence imaging. In total, 100% of the experimental animals developed lymphatic metastasis, the growth of which was monitored in real time by whole-body imaging. The aggressive lymphatic metastasis in this model reflects one of the major metastatic routes of prostate cancer in human patients. Intravital RFP imaging visualized single cancer cells in the lung and bladder. Open RFP imaging at autopsy visualized extensive primary growth and highly disseminated lymph-node metastases.
  
  
  CONCLUSIONS
  The long-wavelength emission of RFP enabled high sensitivity and resolution of microscopic tumor growth using appropriate imaging techniques. The model should be useful for the real-time evaluation of novel therapeutics for metastatic prostate cancer.
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Lingna
authors.initials: L
authors.lastname: Li
authors.forename: Jack
authors.initials: J
authors.lastname: Geller
authors.forename: A R
authors.initials: AR
authors.lastname: Moossa
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D001344:Autopsy; D018450:Disease Progression; D005470:Fluorometry / Q000379:methods / Q000662:veterinary; D005822:Genetic Vectors; D008164:Luminescent Proteins / Q000096:biosynthesis* / Q000235:genetics; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000662:veterinary*; D014183:Transplantation, Heterologous; D000097573:Red Fluorescent Protein
chemical_list: D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein