A Fluorescent Activatable AND‐Gate Chemokine CCL2 Enables In Vivo Detection of Metastasis‐Associated Macrophages

We report the novel chemical design of fluorescent activatable chemokines as highly specific functional probes for imaging subpopulations of immune cells in live tumours. Activatable chemokines behave as AND‐gates since they emit only after receptor binding and intracellular activation, showing enha...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2019-11, Vol.58 (47), p.16894-16898
Main Authors: Fernandez, Antonio, Thompson, Emily J., Pollard, Jeffrey W., Kitamura, Takanori, Vendrell, Marc
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Proliferation
Chemokines
Communication
Communications
Female
Fluorescence
Fluorescent Dyes - chemistry
fluorophores
Humans
imaging
Immune system
immunology
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Macrophages
Macrophages - metabolism
Macrophages - pathology
Metastases
Metastasis
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Imaging - methods
molecular logic
Monocyte chemoattractant protein 1
Organic chemistry
Probes
Receptors, CCR2 - physiology
Selectivity
Spectrometry, Fluorescence
Subpopulations
Tumor Cells, Cultured
Tumors
tumour microenvironment
Xenograft Model Antitumor Assays
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Summary:We report the novel chemical design of fluorescent activatable chemokines as highly specific functional probes for imaging subpopulations of immune cells in live tumours. Activatable chemokines behave as AND‐gates since they emit only after receptor binding and intracellular activation, showing enhanced selectivity over existing agents. We have applied this strategy to produce mCCL2‐MAF as the first probe for in vivo detection of metastasis‐associated macrophages in a preclinical model of lung metastasis. This strategy will accelerate the preparation of new chemokine‐based probes for imaging immune cell function in tumours. Live show: Fluorescent activatable chemokines have been designed as the first chemical probes for in vivo detection of tumour‐associated macrophages in lung metastasis. Activatable chemokines behave as AND gates since they emit only after receptor binding and intracellular activation, thereby showing enhanced selectivity over existing agents.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201910955