DOT corrected fluorescence molecular tomography using targeted contrast agents for small animal tumor imaging
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Updated: May 13, 2026
Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers
Published on: July 17, 2012
Yiyong Tan1, Zehong Cao, Hari Krishna Sajja
1J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611-6131, USA.
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.
Insights
Diffuse optical tomography (DOT) corrected fluorescence molecular tomography (FMT) accurately images tumor-targeted probes in mice. This method detects breast cancer, recurrence, and metastasis, showing potential for early diagnosis.
Area of Science:
- Biomedical Imaging
- Molecular Imaging
- Optical Imaging
Background:
- Accurate quantitative imaging of tumor-targeted contrast agents is crucial for cancer detection and monitoring.
- Fluorescence molecular tomography (FMT) offers high sensitivity but requires correction for accurate quantification.
- Diffuse optical tomography (DOT) can correct for optical scattering and absorption, improving FMT accuracy.
Purpose of the Study:
- To demonstrate DOT-corrected FMT for quantitative imaging of tumor-targeted contrast agents.
- To evaluate the efficacy of novel uPAR-targeted optical imaging probes in a 4T1 mouse mammary tumor model.
- To assess the capability of DOT-corrected FMT in detecting primary tumors, recurrence, and metastasis.
Main Methods:
- Validated DOT-corrected FMT using 4T1 cells labeled with NIR Cy 5.5-ATF-uPA.
- Applied DOT-corrected FMT to image uPAR-targeted NIR-830-ATF-IONP probes in mice with orthotopic 4T1 mammary tumors.
- Compared targeted probes (NIR-830-ATF-IONP) with non-targeted probes (NIR-830-MSA-IONP).
Main Results:
- DOT-corrected FMT accurately quantified and localized injected imaging probes.
- Specific accumulation of uPAR-targeted probes was detected in orthotopic mammary tumors.
- DOT-corrected FMT detected local tumor recurrence and lung metastasis 72 hours post-injection.
Conclusions:
- DOT-corrected FMT provides accurate quantitative imaging of targeted contrast agents.
- uPAR-targeted optical imaging probes demonstrate potential for sensitive breast cancer detection.
- This combined approach shows promise for detecting primary tumors, recurrence, and metastasis in preclinical models.
