Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent

Abstract

The C2 domain of synaptotagmin I, which binds to anionic phospholipids in cell membranes, was shown to bind to the plasma membrane of apoptotic cells by both flow cytometry and confocal microscopy. Conjugation of the protein to superparamagnetic iron oxide nanoparticles allowed detection of this binding using magnetic resonance imaging. Detection of apoptotic cells, using this novel contrast agent, was demonstrated both in vitro, with isolated apoptotic tumor cells, and in vivo, in a tumor treated with chemotherapeutic drugs.

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Figure 1: Etoposide-induced apoptosis in EL4 cells analyzed using flow cytometry and DNA gel electrophoresis.
Figure 2: T2-weighted MRI of cells labeled with protein–SPIO conjugates.
Figure 3: MR images of a tumor in a drug-treated mouse following injection of C2–SPIO (20 mg Fe/kg tissue).
Figure 4: Histological analysis of a tissue section from a slice corresponding to that imaged in the MR experiment shown in Fig. 3.

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Acknowledgements

This work was supported by grants from the Cancer Research Campaign and the Medical Research Council, UK. We would like to thank Ray Hicks for help with the flow cytometry and Lyn Carter and Jeremy Skepper for help with tumor sectioning and confocal microscopy.

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Correspondence to Kevin M. Brindle.

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Zhao, M., Beauregard, D., Loizou, L. et al. Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent. Nat Med 7, 1241–1244 (2001). https://doi.org/10.1038/nm1101-1241

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