In vivo and ex vivo MR imaging of slowly cycling melanoma cells

Abstract

Slowly cycling cells are believed to play a critical role in tumor progression and metastatic dissemination. The goal of this study was to develop a method for in vivo detection of slowly cycling cells. To distinguish these cells from more rapidly proliferating cells that constitute the vast majority of cells in tumors, we used the well‐known effect of label dilution due to division of cells with normal cycle and retention of contrast agent in slowly dividing cells. To detect slowly cycling cells, melanoma cells were labeled with iron oxide particles. After labeling, we observed dilution of contrast agent in parallel with cell proliferation in the vast majority of normally cycling cells. A small and distinct subpopulation of iron‐retaining cells was detected by flow cytometry after 20 days of in vitro proliferation. These iron‐retaining cells exhibited high expression of a biological marker of slowly cycling cells, JARID1B. After implantation of labeled cells as xenografts into immunocompromised mice, iron‐retaining cells were detected in vivo and ex vivo by magnetic resonance imaging that was confirmed by Prussian Blue staining. Magnetic resonance imaging detects not only iron retaining melanoma cells but also iron positive macrophages. Proposed method opens up opportunities to image subpopulation of melanoma cells, which is critical for continuous tumor growth. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.

Imaging of a high concentration of iron labeled cells with positive contrast in a rat knee

“…A determination of the lowest level of grafted cell that can be detected with the proposed method is essential for the clinical translation. In our previous work, we proposed a protocol to determine the sensitivity of T2‐weighted sequences for the detection of the iron oxide particles. We are adopting this technique for the SWIFT acquisition protocol and will report the results in a separate publication.…”

Cellular imaging and texture analysis distinguish differences in cellular dynamics in mouse brain tumors

“…One might anticipate that a simple explanation for the distribution of label in tumors could be that label‐retaining regions contain slowly proliferating cells, while regions that have lost the cellular label represent rapidly dividing cells . Our label distribution maps, in this case, would in essence be cell proliferation maps.…”

“…We use cellular MRI and optical projection tomography (OPT) to map the distribution of a cellular label in two different mouse glioma tumors generated by intracranial injections of labeled tumor cells. The cellular label (iron oxide in the case of MRI ; a fluorescent label in the case of OPT) is diluted over time through cell division and, therefore, lost from quickly dividing cells, but retained in slowly cycling or nonproliferating cells . Consequently, the maps we obtain may reflect differences in the proliferative history of cells throughout the tumor.…”

Investigating the Impact of a Primary Tumor on Metastasis and Dormancy Using MRI: New Insights into the Mechanism of Concomitant Tumor Resistance

“…This is because the iron nanoparticles are diluted over time in dividing cells, leading to loss of signal and therefore loss of cell detection. However, we, and others, have shown that the retention of iron particles in nonproliferative, or slowly cycling, cancer cells can be exploited to detect particular cancer cell populations ( 16 – 18 ). In this paper, we use cellular MRI to study CTR in a novel model of breast cancer metastasis to the brain.…”