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Updated: May 20, 2026
Extended Time-lapse Intravital Imaging of Real-time Multicellular Dynamics in the Tumor Microenvironment
Published on: June 12, 2016
PET imaging of tumor associated macrophages using mannose coated 64Cu liposomes
Landon W Locke1, Marty W Mayo, Alexander D Yoo
1Department of Biomedical Engineering, The University of Virginia, Charlottesville, VA 22908, USA.
Abstract:
Macrophages within the tumor microenvironment (TAMs) have been shown to play a major role in the growth and spread of many types of cancer. Cancer cells produce cytokines that cause macrophages to express scavenger receptors (e.g. the mannose receptor) and factors that facilitate tissue and blood vessel growth, suppress T cell mediated anti-tumor activity, and express enzymes that can break down the extracellular matrix, thereby promoting metastasis. We have designed a mannosylated liposome (MAN-LIPs) and show that it accumulates in TAMs in a mouse model of pulmonary adenocarcinoma. These liposomes are loaded with (64)Cu to allow tracking by PET imaging, and contain a fluorescent dye in the lipid bilayer permitting subsequent fluorescence microscopy. We injected these liposomes into a mouse model of lung cancer. In vivo PET images were acquired 6 h after injection followed by the imaging of select excised organs. MAN-LIPs accumulated in TAMs and exhibited little accumulation in remote lung areas. MAN-LIPs are a promising new vehicle for the delivery of imaging agents to lung TAMs. In addition to imaging, MAN-LIPs hold the potential for delivery of therapeutic agents to the tumor microenvironment.
Insights
Mannosylated liposomes (MAN-LIPs) effectively target tumor-associated macrophages (TAMs) in lung cancer models. This novel delivery system shows potential for both imaging and therapeutic agent delivery to the tumor microenvironment.
Area of Science:
- Oncology
- Nanotechnology
- Immunology
Background:
- Tumor-associated macrophages (TAMs) are crucial in cancer progression, promoting tumor growth, angiogenesis, immune suppression, and metastasis.
- TAMs express scavenger receptors, such as the mannose receptor, which can be targeted for drug and imaging agent delivery.
Purpose of the Study:
- To design and evaluate mannosylated liposomes (MAN-LIPs) as a targeted delivery vehicle for imaging agents to TAMs in a lung cancer model.
- To assess the accumulation and distribution of MAN-LIPs in TAMs using PET imaging and fluorescence microscopy.
Main Methods:
- Development of (64)Cu-loaded, fluorescently labeled mannosylated liposomes (MAN-LIPs).
- Administration of MAN-LIPs to a mouse model of pulmonary adenocarcinoma.
- In vivo positron emission tomography (PET) imaging at 6 hours post-injection.
- Ex vivo imaging of excised organs using fluorescence microscopy.
Main Results:
- MAN-LIPs demonstrated significant accumulation within TAMs in the lung cancer model.
- High accumulation of MAN-LIPs was observed in TAMs, with minimal uptake in healthy lung tissue.
- PET imaging effectively tracked the in vivo distribution of MAN-LIPs.
Conclusions:
- Mannosylated liposomes (MAN-LIPs) are a promising platform for targeted delivery of imaging agents to lung TAMs.
- MAN-LIPs hold potential for theranostic applications, enabling both diagnosis and therapy delivery to the tumor microenvironment.
