title: DOT corrected fluorescence molecular tomography using targeted contrast agents for small animal tumor imaging.
abstract: OBJECTIVE
  To demonstrate diffuse optical tomography (DOT) corrected fluorescence molecular tomography (FMT) for quantitatively imaging tumor-targeted contrast agents in a 4T1 mouse mammary tumor model.
  
  
  METHODS
  In the first set of experiments, we validated our DOT corrected FMT method using subcutaneously injected 4T1 cells pre-labeled with a near-infrared (NIR) Cy 5.5 dye labeled recombinant amino-terminal fragment (ATF) of the receptor binding domain of urokinase plasminogen activator (uPA), which binds to uPA receptor (uPAR) that is highly expressed in breast cancer tissues. Next, we apply the DOT corrected FMT method to quantitatively evaluate the ability of sensitive tumor imaging after systemic delivery of new uPAR-targeted optical imaging probes in the mice bearing 4T1 mammary tumors. These uPAR-targeted optical imaging probes are ATF peptides labeled with a newly developed NIR-830 dye being conjugated to magnetic iron oxide nanoparticles (IONPs).
  
  
  RESULTS
  Our results have shown that DOT corrected FMT can accurately quantify and localize the injected imaging probe labeled 4T1 cells. Following systemic delivery of the targeted imaging nanoprobes into the mice bearing orthotopic mammary tumors, specific accumulation of the imaging probes in the orthotopic mammary tumors was detected in the mice that received uPAR targeted NIR-830-ATF-IONP probes but not in the mice injected with non-targeted NIR-830-mouse serum albumin (MSA)-IONPs. Additionally, DOT corrected FMT also enables the detection of both locally recurrent tumor and lung metastasis in the mammary tumor model 72 hrs after systemic administration of the uPAR-targeted NIR-830-labeled ATF peptide imaging probes.
  
  
  CONCLUSIONS
  DOT corrected FMT and uPAR-targeted optical imaging probes have great potential for detection of breast cancer, recurrent tumor and metastasis in small animals.
authors.affiliation: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611-6131, USA.
authors.forename: Yiyong
authors.initials: Y
authors.lastname: Tan
authors.forename: Zehong
authors.initials: Z
authors.lastname: Cao
authors.forename: Hari Krishna
authors.initials: HK
authors.lastname: Sajja
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Lipowska
authors.forename: Y Andrew
authors.initials: YA
authors.lastname: Wang
authors.forename: Lily
authors.initials: L
authors.lastname: Yang
authors.forename: Huabei
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D061848:Optical Imaging / Q000379:methods*; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism; D041622:Tomography, Optical / Q000379:methods*; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D051598:Whole Body Imaging / Q000379:methods
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D003287:Contrast Media; D005456:Fluorescent Dyes; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator