WE-C-217BCD-04: Multimodality Imaging of Breast Cancer Experimental Lung Metastasis

Area of Science:

• Oncology
• Medical Imaging
• Molecular Biology

Background:

• Metastatic breast cancer (MBC) is currently incurable.
• CD 105 staining is the clinical standard for assessing tumor microvessel density (MVD), a key prognostic marker in MBC.
• Non-invasive imaging of MVD and CD105 expression is needed for improved MBC management.

Purpose of the Study:

• To develop a dual positron emission tomography (PET)/near-infrared fluorescent (NIRF) imaging probe for CD105 expression in MBC.
• To enable non-invasive measurement of MVD in MBC.
• To explore applications in early metastasis detection and intraoperative guidance.

Main Methods:

• Dual-labeling of anti-CD105 mAb TRC105 with 89Zr and a NIRF dye (800CW) to create 89Zr-Df-TRC105-800CW.
• Establishment of a lung MBC model using luciferase-transfected 4T1 cells in mice.
• In vivo/ex vivo studies including PET, NIRF imaging, bioluminescence imaging (BLI), biodistribution, blocking studies, and histology.

Main Results:

• 89Zr-Df-TRC105-800CW demonstrated high tumor uptake and excellent contrast in a murine MBC model.
• PET imaging showed significant tumor uptake at 4, 24, and 48 hours post-injection.
• Specificity for CD105 was confirmed through various control studies and histology.
• The probe also showed potential for imaging other cancer types and guided tumor removal in a subcutaneous model.

Conclusions:

• The study reports the first successful PET/NIRF imaging of CD105 expression in an MBC model.
• TRC105-based agents exhibit broad clinical potential across multiple tumor types.
• The developed probe facilitates early detection of metastases and intraoperative guidance for tumor resection.