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Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo.

ABSTRACT: A solid tumor is an organ composed of cancer and host cells embedded in an extracellular matrix and nourished by blood vessels. A prerequisite to understanding tumor pathophysiology is the ability to distinguish and monitor each component in dynamic studies. Standard fluorophores hamper simultaneous intravital imaging of these components. Here, we used multiphoton microscopy techniques and transgenic mice that expressed green fluorescent protein, and combined them with the use of quantum dot preparations. We show that these fluorescent semiconductor nanocrystals can be customized to concurrently image and differentiate tumor vessels from both the perivascular cells and the matrix. Moreover, we used them to measure the ability of particles of different sizes to access the tumor. Finally, we successfully monitored the recruitment of quantum dot-labeled bone marrow-derived precursor cells to the tumor vasculature. These examples show the versatility of quantum dots for studying tumor pathophysiology and creating avenues for treatment.

SUBMITTER: Stroh M

PROVIDER: S-EPMC2686110 | biostudies-literature | 2005 Jun

REPOSITORIES: biostudies-literature

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Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo.

Stroh Mark M Zimmer John P JP Duda Dan G DG Levchenko Tatyana S TS Cohen Kenneth S KS Brown Edward B EB Scadden David T DT Torchilin Vladimir P VP Bawendi Moungi G MG Fukumura Dai D Jain Rakesh K RK

Nature medicine 20050508 6

A solid tumor is an organ composed of cancer and host cells embedded in an extracellular matrix and nourished by blood vessels. A prerequisite to understanding tumor pathophysiology is the ability to distinguish and monitor each component in dynamic studies. Standard fluorophores hamper simultaneous intravital imaging of these components. Here, we used multiphoton microscopy techniques and transgenic mice that expressed green fluorescent protein, and combined them with the use of quantum dot pre ...[more]

PMID: 15880117

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Project description:INTRODUCTION:The detection of circulating tumor cells (CTCs) is very important for cancer diagnosis. CTCs can travel from primary tumors through the circulation to form secondary tumor colonies via bloodstream extravasation. The number of CTCs has been used as an indicator of cancer progress. However, the population of CTCs is very heterogeneous. It is very challenging to identify CTC subpopulations such as cancer stem cells (CSCs) with high metastatic potential, which are very important for cancer diagnostic management. RESULTS:We report a study of real-time CTC and CSC imaging in the bloodstreams of living animals using multi-photon microscopy and antibody conjugated quantum dots. We have developed a cancer model for noninvasive imaging wherein pancreatic cancer cells expressing fluorescent proteins were subcutaneously injected into the earlobes of mice and then formed solid tumors. When the cancer cells broke away from the solid tumor, CTCs with fluorescent proteins in the bloodstream at different stages of development could be monitored noninvasively in real time. The number of CTCs observed in the blood vessels could be correlated to the tumor size in the first month and reached a maximum value of approximately 100 CTCs/min after 5 weeks of tumor inoculation. To observe CTC subpopulations, conjugated quantum dots were used. It was found that cluster of differentiation (CD)24+?CTCs can move along the blood vessel walls and migrate to peripheral tissues. CD24+?cell accumulation on the solid tumors' sides was observed, which may provide valuable insight for designing new drugs to target cancer subpopulations with high metastatic potential. We also demonstrated that our system is capable of imaging a minor population of cancer stem cells, CD133+?CTCs, which are found in 0.7% of pancreatic cancer cells and 1%-3% of solid tumors in patients. CONCLUSIONS:With the help of quantum dots, CTCs with higher metastatic potential, such as CD24+?and CD133+?CTCs, have been identified in living animals. Using our approach, it may be possible to investigate detailed metastatic mechanism such as tumor cell extravasation to the blood vessels. In addition, the number of observed CTCs in the blood stream could be correlated with tumor stage in the early stage of cancer.

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Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo.

Publications

Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo.

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