Multimodal cell tracking of a spontaneous metastasis model: comparison between MRI, electron paramagnetic resonance and bioluminescence

Abstract

MRI cell tracking is a promising technique for tracking various cell types in living animals. Usually, cells are incubated with iron oxides so that the particles are taken up before the cells are injected in vivo. In the present study, we aimed to monitor migration of luciferase-expressing mouse renal cancer cells (RENCA-luc) after intrarenal or intrasplenic injection. These cells were labelled using Molday Ion Rhodamine B (MIRB) fluorescent superparamagnetic iron oxide particles. Their fate after injection was first assessed using ex vivo X-band electron paramagnetic resonance (EPR) spectroscopy. This biodistribution study showed that RENCA-luc cells quickly colonized the lungs and the liver after intrarenal and intrasplenic injection, respectively. Bioluminescence imaging (BLI) studies confirmed that this cell line preferentially metastasized to these organs. Early tracking of labelled RENCA-luc cells in the liver using high-field MRI (11.7 T) was not feasible because of a lack of sensitivity. MRI of MIRB-labelled RENCA-luc cells after injection in the left kidney was then performed. T 2 -and T 2 *-weighted images showed that the labelled cells induced hypointense signals at the injection site. Nevertheless, the hypointense regions tended to disappear after several days, mainly owing to dilution of the MIRB iron oxides with cell proliferation. In conclusion, EPR is well adapted to ex vivo analysis of tissues after cell tracking experiments and allows short-term monitoring of metastasizing cells. MRI is a suitable tool for checking labelled cells at their injection site, but dilution of the iron oxides owing to cell division remains a major limitation. BLI remains the most suitable technique for long-term monitoring of metastatic cells.

Tumor Targeting by RGD-Grafted PLGA-Based Nanotheranostics Loaded with Paclitaxel and Superparamagnetic Iron Oxides

“…ESR is a spectrometric technique that is used to study free radicals and (super) paramagnetic molecules. The ESR method was shown to be sensitive and specific for the iron oxide content determination in biological samples [16,21]. SPIO present a typical broad ESR spectrum at room temperature that can be differentiated from free Fe +++ ion.…”

“…For this reason, inductively coupled plasma mass spectroscopy (ICP-MS) was used to validate the ESR technique [16] (see section 3.1.4). Unlike ESR, ICP-MS is not specific for SPIO and measures the total iron content in samples [16,21]. ESR was used in several studies to measure in vitro and ex vivo the iron oxide content in cells and rodent tissues such as the liver, the brain, the lungs, the kidneys, and tumor tissues, while ICP-MS cannot [21,22].…”

“…Previously, ESR has already been described for studying iron oxide particles, mainly to characterize their physicochemical properties or to measure their distribution in tissues after systemic injection [21]. For the characterization of new SPIO formulations using ESR spectroscopy, a calibration curve using several dilutions of iron oxides is mandatory to precisely determine the iron oxide content of samples.…”

“…For the characterization of new SPIO formulations using ESR spectroscopy, a calibration curve using several dilutions of iron oxides is mandatory to precisely determine the iron oxide content of samples. Of note, iron oxides used for the calibration must share similar physicochemical properties than those contained in the samples [16,21]. For this reason, inductively coupled plasma mass spectroscopy (ICP-MS) was used to validate the ESR technique [16] (see section 3.1.4).…”

Multispectral Emissions of Lanthanide-Doped Gadolinium Oxide Nanophosphors for Cathodoluminescence and Near-Infrared Upconversion/Downconversion Imaging

“…In recent years, multimodal imaging has attracted tremendous attention among researchers in varied fields [1,2,3,4,5,6,7,8]. The principal merit of multimodalities is the capability of each modality to synergistically and significantly compensate for the limitations of the others.…”