Affiliations: J. Crayton Pruitt Family Department of Biomedical
Engineering, University of Florida, Gainesville, FL, USA | Departments of Surgery, Emory University, Atlanta, GA,
USA | Departments of Radiology, Emory University, Atlanta,
GA, USA | Oceannanotech LLC, Springdale, AR, USA
Note: [] Corresponding authors: Huabei Jiang, J. Crayton Pruitt Family
Department of Biomedical Engineering University of Florida JG-56 Biomedical
Sciences Building | P.O. Box 116131 Gainesville, FL 32611-6131, USA. E-mail:
hjiang@bme.ufl.edu. Lily Yang, Departments of Surgery Emory University,
Atlanta, GA 30322, USA. E-mail: lyang02@emory.edu
Abstract: PURPOSE: 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. PROCEDURES: 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.
