Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy

Abstract

Metastasis is an impediment to the development of effective cancer therapies. Our understanding of metastasis is limited by our inability to follow this process in vivo. Fluorescence microscopy offers the potential to follow cells at high resolution in living animals. Semiconductor nanocrystals, quantum dots (QDs), offer considerable advantages over organic fluorophores for this purpose. We used QDs and emission spectrum scanning multiphoton microscopy to develop a means to study extravasation in vivo. Although QD labeling shows no deleterious effects on cultured cells, concern over their potential toxicity in vivo has caused resistance toward their application to such studies. To test if effects of QD labeling emerge in vivo, tumor cells labeled with QDs were intravenously injected into mice and followed as they extravasated into lung tissue. The behavior of QD-labeled tumor cells in vivo was indistinguishable from that of unlabeled cells. QDs and spectral imaging allowed the simultaneous identification of five different populations of cells using multiphoton laser excitation. Besides establishing the safety of QDs for in vivo studies, our approach permits the study of multicellular interactions in vivo.

In vivo monitoring of multiple circulating cell populations using two-photon flow cytometry

“…Both cell lines retained their detectability level in vivo when the quantum dot assignments were switched, indicating that the measured kinetics of each cell line were not biased by the emission wavelength of quantum dots. These data are consistent with prior work showing that behavior of quantum dot-labeled tumor cells and unlabeled cells in vivo are indistinguishable following tail vein injection [13].…”

In vivo quantum dot labeling of mammalian stem and progenitor cells

“…Several studies have shown that multiple-spectra QDs can be used to achieve coincident tracking of multiple tumor cells in vivo using fluorescence emission-scanning microscopy (Gao et al, 2004;. In the central nervous system, microangiography of deep brain blood vessels and nonspecific labeling of brain cells has been achieved following QD injection into arterial blood (Levene et al, 2004;Voura et al, 2004).…”

Exploiting nanotechnology to target cancer

“…Furthermore, labelling the tumour cells with Qdots also enabled the tracking of metastatic tumour cell extravasation (Voura et al, 2004). The last study also established the safety profile of Qdots in vivo, although extensive safety and pharmacokinetics studies need to be carried out before use in humans given the fact that Qdots are composed of heavy metals (such as Cd), which can induce liver and kidney damage.…”