title: In-vivo near-infrared optical imaging of growing osteosarcoma cell lesions xenografted in mice: dual-channel quantitative evaluation of volume and mineralization.
abstract: BACKGROUND
  In a previous study using a rodent osteosarcoma-grafted rat model, in which cell-dependent mineralization was previously demonstrated to proportionally increase with growth, we performed a quantitative analysis of mineral deposit formation using (99m)Tc-HMDP and found some weaknesses, such as longer acquisition time and narrower dynamic ranges (i.e. images easily saturated). The recently developed near-infrared (NIR) optical imaging technique is expected to non-invasively evaluate changes in living small animals in a quantitative manner.
  
  
  OBJECTIVE
  To test the feasibility of NIR imaging with a dual-channel system as a better alternative for bone scintigraphy by quantitatively evaluating mineralization along with the growth of osteosarcoma lesions in a mouse-xenograft model.
  
  
  METHODS
  The gross volume and mineralization of osteosarcoma lesions were evaluated in living mice simultaneously with dual-channels by NIR dye-labeled probes, 2-deoxyglucose (DG) and pamidronate (OS), respectively. To verify these quantitative data, retrieved osteosarcoma lesions were then subjected to ex-vivo imaging, weighing under wet conditions, microfocus-computed tomography (μCT) analysis, and histopathological examination.
  
  
  RESULTS
  Because of less scattering and no anatomical overlapping, as generally shown, specific fluorescence signals targeted to the osteosarcoma lesions could be determined clearly by ex-vivo imaging. These data were well positively correlated with the in-vivo imaging data (r > 0.8, P < 0.02). Other good to excellent correlations (r > 0.8, P < 0.02) were observed between DG accumulation and tumor gross volume and between OS accumulation and mineralization volume.
  
  
  CONCLUSIONS
  This in-vivo NIR imaging technique using DG and OS is sensitive to the level to simultaneously detect and quantitatively evaluate the growth and mineralization occuring in this type of osteosarcoma lesions of living mice without either invasion or sacrifice. By possible mutual complementation, this dual imaging system might be useful for accurate diagnosis even in the presence of overlapping tissues.
authors.affiliation: Division of Oral Bioengineering, Department of Tissue Regeneration and Reconstitution, Institute of Medicine and Dentistry, Niigata University, Niigata, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakayama
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawase
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Okuda
authors.forename: Larry F
authors.initials: LF
authors.lastname: Wolff
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yoshie
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology* / Q000503:physiopathology; D002113:Calcification, Physiologic / Q000502:physiology*; D004164:Diphosphonates; D005240:Feasibility Studies; D007294:Inositol / Q000031:analogs & derivatives; D051379:Mice; D008812:Mice, Hairless; D012516:Osteosarcoma / Q000473:pathology* / Q000503:physiopathology; D000077268:Pamidronate; D019275:Radiopharmaceuticals; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013669:Technetium Tc 99m Medronate / Q000031:analogs & derivatives; D014183:Transplantation, Heterologous
chemical_list: D004164:Diphosphonates; D019275:Radiopharmaceuticals; D007294:Inositol; C075548:2-deoxyinosose; C024226:technetium Tc 99m hydroxymethylene diphosphonate; D000077268:Pamidronate; D013669:Technetium Tc 99m Medronate