PMID- 23507851 OWN - NLM STAT- MEDLINE DCOM- 20130909 LR - 20211021 IS - 1095-9114 (Electronic) IS - 0895-3996 (Print) IS - 0895-3996 (Linking) VI - 21 IP - 1 DP - 2013 TI - DOT corrected fluorescence molecular tomography using targeted contrast agents for small animal tumor imaging. PG - 43-52 LID - 10.3233/XST-130365 [doi] AB - 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. FAU - Tan, Yiyong AU - Tan Y AD - J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611-6131, USA. FAU - Cao, Zehong AU - Cao Z FAU - Sajja, Hari Krishna AU - Sajja HK FAU - Lipowska, Malgorzata AU - Lipowska M FAU - Wang, Y Andrew AU - Wang YA FAU - Yang, Lily AU - Yang L FAU - Jiang, Huabei AU - Jiang H LA - eng GR - R01 CA133722/CA/NCI NIH HHS/United States GR - R01 CA154129/CA/NCI NIH HHS/United States GR - R01 CA154846/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - Netherlands TA - J Xray Sci Technol JT - Journal of X-ray science and technology JID - 9000080 RN - 0 (CY5.5 cyanine dye) RN - 0 (Carbocyanines) RN - 0 (Contrast Media) RN - 0 (Fluorescent Dyes) RN - 0 (Receptors, Urokinase Plasminogen Activator) RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) SB - IM MH - Animals MH - Carbocyanines/chemistry/pharmacokinetics MH - Cell Line, Tumor MH - Contrast Media/chemistry/*pharmacokinetics MH - Female MH - Fluorescent Dyes/chemistry/pharmacokinetics MH - Image Processing, Computer-Assisted MH - Mice MH - Mice, Inbred BALB C MH - Neoplasms, Experimental/metabolism/*pathology MH - Optical Imaging/*methods MH - Receptors, Urokinase Plasminogen Activator/metabolism MH - Tomography, Optical/*methods MH - Urokinase-Type Plasminogen Activator/chemistry/metabolism/pharmacokinetics MH - Whole Body Imaging/methods PMC - PMC3785613 MID - NIHMS496930 EDAT- 2013/03/20 06:00 MHDA- 2013/09/10 06:00 PMCR- 2014/01/01 CRDT- 2013/03/20 06:00 PHST- 2013/03/20 06:00 [entrez] PHST- 2013/03/20 06:00 [pubmed] PHST- 2013/09/10 06:00 [medline] PHST- 2014/01/01 00:00 [pmc-release] AID - 30605P6420828713 [pii] AID - 10.3233/XST-130365 [doi] PST - ppublish SO - J Xray Sci Technol. 2013;21(1):43-52. doi: 10.3233/XST-130365.