scholarly journals The sensitivity of magnetic particle imaging and fluorine-19 magnetic resonance imaging for cell tracking

2021 ◽  
Author(s):  
Olivia C. Sehl ◽  
Paula J. Foster
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Tracking ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Cell Detection ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

AbstractPurposeMagnetic particle imaging (MPI) and fluorine-19 (19F) MRI produce images which allow for quantification of labeled cells. MPI is an emerging instrument for cell tracking, which is expected to have superior sensitivity compared to 19F MRI. Our objective is to assess the cellular sensitivity of MPI and 19F MRI for detection of mesenchymal stem cells (MSC) and breast cancer cells.MethodsCells were labeled with ferucarbotran or perfluoropolyether, for imaging on a preclinical MPI system or 3 Tesla clinical MRI, respectively. In vivo sensitivity with MPI and 19F MRI was evaluated by imaging MSC that were administered by different routes.ResultsUsing the same imaging time, as few as 4000 MSC (76 ng iron) and 8000 breast cancer cells (74 ng iron) were reliably detected with MPI, and 256,000 MSC (9.01 × 101619F atoms) were detected with 19F MRI, with SNR > 5. In vivo imaging revealed reduced sensitivity compared to ex vivo cell pellets of the same cell number.ConclusionMPI has the potential to be more sensitive than 19F MRI for cell tracking. We attribute reduced MPI and 19F MRI cell detection in vivo to the effect of cell dispersion among other factors, which are described.

scholarly journals The sensitivity of magnetic particle imaging and fluorine-19 magnetic resonance imaging for cell tracking

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Olivia C. Sehl ◽  
Paula J. Foster
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Tracking ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Cell Detection ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

AbstractMagnetic particle imaging (MPI) and fluorine-19 (19F) MRI produce images which allow for quantification of labeled cells. MPI is an emerging instrument for cell tracking, which is expected to have superior sensitivity compared to 19F MRI. Our objective is to assess the cellular sensitivity of MPI and 19F MRI for detection of mesenchymal stem cells (MSC) and breast cancer cells. Cells were labeled with ferucarbotran or perfluoropolyether, for imaging on a preclinical MPI system or 3 Tesla clinical MRI, respectively. Using the same imaging time, as few as 4000 MSC (76 ng iron) and 8000 breast cancer cells (74 ng iron) were reliably detected with MPI, and 256,000 MSC (9.01 × 1016 19F atoms) were detected with 19F MRI, with SNR > 5. MPI has the potential to be more sensitive than 19F MRI for cell tracking. In vivo sensitivity with MPI and 19F MRI was evaluated by imaging MSC that were administered by different routes. In vivo imaging revealed reduced sensitivity compared to ex vivo cell pellets of the same cell number. We attribute reduced MPI and 19F MRI cell detection in vivo to the effect of cell dispersion among other factors, which are described.

scholarly journals Development of Magnetic Particle Imaging (MPI) for Cell Tracking and Detection

2020 ◽  
Author(s):  
Kierstin P Melo ◽  
Ashley V Makela ◽  
Natasha N Knier ◽  
Amanda M Hamilton ◽  
Paula J Foster
Keyword(s):  
Iron Content ◽  
Cell Tracking ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Imaging Modality ◽  
Superparamagnetic Iron Oxide ◽  
Cell Injection ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

AbstractIntroductionMagnetic particle imaging (MPI) is a new imaging modality that sensitively and specifically detects superparamagnetic iron oxide nanoparticles (SPIONs) within a sample. SPION-based MRI cell tracking has very high sensitivity, but low specificity and quantification of iron labeled cells is difficult. MPI cell tracking could overcome these challenges.MethodsMDM-AB-231BR cells labeled with MPIO, mice were intracardially injected with either 2.5 × 105 or 5.0 × 105 cells. MRI was performed in vivo the same day at 3T using a bSSFP sequence. After mice were imaged ex vivo with MPI. In a second experiment Mice received an intracardiac injection of either 2.5 × 10 5 or 5 × 10 4 MPIO-labeled 231BR cells. In a third experiment, mice were injected with 5 × 10 4 4T1BR cells, labelled with either MPIO or the SPION Vivotrax. MRI and MPI was performed in vivo.ResultsSignal from MPI and signal voids from MRI both showed more iron content in mice receiving an injection of 5.0 × 105 cells than the 2.5 × 105 injection. In the second experiment, Day 0 MRI showed signal voids and MPI signal was detected in all mouse brains. The MPI signal and iron content measured in the brains of mice that were injected with 2.5 × 10 5 cells were approximately four times greater than in brains injected with 5 × 10 4 cells. In the third experiment, in vivo MRI was able to detect signal voids in the brains of mice injected with Vivotrax and MPIO, although voids were fainter in Vivotrax labeled cells. In vivo MPI signal was only detectable in mice injected with MPIO-labeled cells.ConclusionThis is the first example of the use of MPIO for cell tracking with MPI. With an intracardiac cell injection, approximately 15% of the injected cells are expected to arrest in the brain vasculature. For our lowest cell injection of 5.0 × 104 cells this is ∼10000 cells.

In vivo visualization and ex vivo quantification of murine breast cancer cells in the mouse brain using MRI cell tracking and electron paramagnetic resonance

2015 ◽  
Vol 28 (3) ◽  
pp. 367-375 ◽  
Author(s):  
Pierre Danhier ◽  
Julie Magat ◽  
Philippe Levêque ◽  
Géraldine De Preter ◽  
Paolo E. Porporato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Electron Paramagnetic Resonance ◽  
Cancer Cells ◽  
Mouse Brain ◽  
Breast Cancer Cells ◽  
Cell Tracking ◽  
Ex Vivo ◽  
Paramagnetic Resonance ◽  
Electron Paramagnetic

scholarly journals Targeting of prostate-specific membrane antigen for radio-ligand therapy of triple-negative breast cancer

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Agnieszka Morgenroth ◽  
Ebru Tinkir ◽  
Andreas T. J. Vogg ◽  
Ramya Ambur Sankaranarayanan ◽  
Fatima Baazaoui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Ex Vivo ◽  
Tube Formation ◽  
Huvec Cells ◽  
Specific Membrane

Abstract Background Triple-negative breast cancer has extremely high risk of relapse due to the lack of targeted therapies, intra- and inter-tumoral heterogeneity, and the inherent and acquired resistance to therapies. In this study, we evaluate the potential of prostate-specific membrane antigen (PSMA) as target for radio-ligand therapy (RLT). Methods Tube formation was investigated after incubation of endothelial HUVEC cells in tumor-conditioned media and monitored after staining using microscopy. A binding study with 68Ga-labeled PSMA-addressing ligand was used to indicate targeting potential of PSMA on tumor-conditioned HUVEC cells. For mimicking of the therapeutic application, tube formation potential and vitality of tumor-conditioned HUVEC cells were assessed following an incubation with radiolabeled PSMA-addressing ligand [177Lu]-PSMA-617. For in vivo experiments, NUDE mice were xenografted with triple-negative breast cancer cells MDA-MB231 or estrogen receptor expressing breast cancer cells MCF-7. Biodistribution and binding behavior of [68Ga]-PSMA-11 was investigated in both tumor models at 30 min post injection using μPET. PSMA- and CD31-specific staining was conducted to visualize PSMA expression and neovascularization in tumor tissue ex vivo. Results The triple-negative breast cancer cells MDA-MB231 showed a high pro-angiogenetic potential on tube formation of endothelial HUVEC cells. The induced endothelial expression of PSMA was efficiently addressed by radiolabeled PSMA-specific ligands. 177Lu-labeled PSMA-617 strongly impaired the vitality and angiogenic potential of HUVEC cells. In vivo, as visualized by μPET, radiolabeled PSMA-ligand accumulated specifically in the triple-negative breast cancer xenograft MDA-MB231 (T/B ratio of 43.3 ± 0.9), while no [68Ga]-PSMA-11 was detected in the estrogen-sensitive MCF-7 xenograft (T/B ratio of 1.1 ± 0.1). An ex vivo immunofluorescence analysis confirmed the localization of PSMA on MDA-MB231 xenograft-associated endothelial cells and also on TNBC cells. Conclusions Here we demonstrate PSMA as promising target for two-compartment endogenous radio-ligand therapy of triple-negative breast cancer.

scholarly journals Tracking Adoptive T Cell Therapy Using Magnetic Particle Imaging

2020 ◽  
Author(s):  
Angelie Rivera-Rodriguez ◽  
Lan B. Hoang-Minh ◽  
Andreina Chiu-Lam ◽  
Nicole Sarna ◽  
Leyda Marrero-Morales ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Solid Tumors ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Intraventricular Administration ◽  
Magnetic Particle Imaging ◽  
Particle Imaging ◽  
The Brain

ABSTRACTAdoptive cellular therapy (ACT) is a potent strategy to boost the immune response against cancer. ACT is an effective treatment for blood cancers, such as leukemias and lymphomas, but faces challenges treating solid tumors and cancers in locations like the brain. A critical step for success of ACT immunotherapy is achieving efficient trafficking of T cells to solid tumors, and the non-invasive and quantitative tracking of adoptively transferred T cell biodistribution would accelerate its development. Here, we demonstrate the use of Magnetic Particle Imaging (MPI) to non-invasively track ACT T cells in vivo. Labeling T cells with the superparamagnetic iron oxide nanoparticle tracer ferucarbotran did not affect T cell viability, phenotype, or cytotoxic function in vitro. Following ACT, ferucarbotran-labeled T cells were detected and quantified using MPI ex vivo and in vivo, in a mouse model of invasive brain cancer. Proof-of-principle in vivo MPI demonstrated its capacity to detect labeled T cells in lungs and liver after intravenous administration and to monitor T cell localization in the brain after intraventricular administration. Ex vivo imaging using MPI and optical imaging suggests accumulation of systemically administered ferucarbotran-labeled T cells in the brain, where MPI signal from ferucarbotran tracers and fluorescently tagged T cells were observed. Ex vivo imaging also suggest differential accumulation of nanoparticles and viable T cells in other organs like the spleen and liver. These results support the use of MPI to track adoptively transferred T cells and accelerate the development of ACT treatments for brain tumors and other cancers.

529 Cancer cells educate natural killer cells to a metastasis promoting cell state

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A565-A565
Author(s):  
Isaac Chan ◽  
Hildur Knútsdóttir ◽  
Gayathri Ramakrishnan ◽  
Veena Padmanaban ◽  
Manisha Warrier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nk Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Nk Cell ◽  
Ex Vivo ◽  
Tumor Bearing ◽  
Growth Promoting ◽  
Tumor Organoids

BackgroundMetastatic disease drives breast cancer mortality. We recently discovered that leading cells at the invasive edge of mammary tumor organoids retain a conserved basal epithelial program defined by their expression of keratin-14 (K14), establishing K14 as a good marker of invasive breast cancer cells. K14-positive invasive cells also exhibit characteristics that make them targets of immunosurveillance by natural killer (NK) cells. While NK cells are key immune mediators in the control of metastasis, our understanding of the specific mechanisms behind this regulation and its eventual evasion by metastatic cells remains incomplete.MethodsWe have developed a novel preclinical 3D co-culture assay to discover mechanisms behind interactions between K14+ invasive breast cancer cells and NK cells. Combined with in vivo assays of metastasis, we are able to determine how NK cells limit the early stages of metastasis and also how tumor cells can influence key NK cell properties.ResultsIn ex vivo co-culture assays of NK cells isolated from healthy mouse donors and mammary tumor organoids from MMTV-PyMT and C31T mouse models of breast cancer, we demonstrate that NK cells limit the early stages of metastasis. Antibodies to invasive K14+ cells were able to enhance the ability of NK cells to limit colony formation, suggesting antibody-dependent cell mediated cytotoxicity. Surprisingly, when isolated from tumor bearing mice, NK cells did not limit invasion and instead promoted colony formation. The in vivo adoptive transfer of NK cells from healthy donors prevents the progression of early lung metastatic seeds to macrometastases, while the adoptive transfer of cells isolated from tumor bearing donors promotes macrometastatic development. Transcriptomic analysis of reprogrammed NK cells demonstrate they have similar profiles to resting NK cells. This growth promoting phenotype can be reversed with antibodies targeting inhibitory cell surface receptors or the epigenome.ConclusionsOur ex vivo and in vivo data demonstrate that healthy donor NK cells can limit metastasis through the directed cytotoxicity against pioneering K14+ invasive cells. However, prolonged exposure to tumors reprogram NK cells from tumor killing to tumor promoting, specifically in promoting the outgrowth of macrometastases. Further, we can neutralize this effect using NK cell specific inhibitory antibodies and epigenetic modifiers. This is the first time inhibitory signaling on NK cells have been linked with a growth promoting phenotype. These data can provide insight into when the use of NK cell directed therapies can be used to treat or prevent clinically relevant metastatic disease.

scholarly journals Tracking the fates of iron-labeled tumor cells in vivo using Magnetic Particle Imaging

2021 ◽  
Author(s):  
Ashley V Makela ◽  
Melissa A Schott ◽  
Olivia C Sehl ◽  
Julia J Gevaert ◽  
Paula J. Foster ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cancer Progression ◽  
Cell Tracking ◽  
Magnetic Particle ◽  
Immune Escape ◽  
Positive Contrast ◽  
Magnetic Particle Imaging ◽  
Anatomic Locations ◽  
Particle Imaging

The use of imaging to detect and monitor the movement and accumulation of cells in living subjects can provide significant insights that can improve our understanding of metastasis and guide therapeutic development. For cell tracking using Magnetic Resonance Imaging (MRI), cells are labeled with iron oxides and the effects of the iron on water provides contrast. However, due to low specificity and difficulties in quantification with MRI, other modalities and approaches need to be developed. Magnetic Particle Imaging (MPI) is an emerging imaging technique which directly detects magnetic iron, allowing for a specific, quantitative and sensitive readout. Here, we use MPI to image iron-labeled tumor cells longitudinally, from implantation and growth at a primary site to movement to distant anatomic sites. In vivo bioluminescent imaging (BLI) was used to identify tumor metastases and computed tomography (CT) allowed for correlation of these signals to anatomic locations. These three imaging modalities provide information on immune escape and metastasis of iron-labeled, and unlabeled, tumor cells, and the accumulation of cell-free iron contrast over time. We identified iron signals by MPI and tumor cells via BLI, and correlated these positive contrast images with CT scans to reveal the anatomic sites with cancer cells; histologic analysis confirmed the presence of iron-labeled tumor cells in the tissues, suggesting that the metastatic cells retained enough iron for MPI detection. The use of multi-modality cell tracking reveals the movement, accumulation and fates of labeled cells that will be helpful understanding cancer progression and guiding the development targeted therapies.

scholarly journals Magnetic Particle Imaging is a sensitive in vivo imaging modality for the quantification of dendritic cell migration

2021 ◽  
Author(s):  
Julia J Gevaert ◽  
Corby Fink ◽  
Jimmy D. Dikeakos ◽  
Gregory A. Dekaban ◽  
Paula J Foster
Keyword(s):  
Dendritic Cell ◽  
Lymph Nodes ◽  
In Vivo Imaging ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Imaging Modality ◽  
Cellular Mri ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

Immunotherapies, such as dendritic cell- (DC-)based therapies, are useful for treating cancer as an alternative to or in combination with traditional therapies. Cells must migrate to lymphoid organs to be effective and the magnitude of the ensuing T cell response is proportional to the number of lymph node-migrated DC. With less than 10% of cells expected to reach their destination, there is a need for an imaging modality capable of sensitively and quantitatively detecting cells. MRI has been used to track DC using iron and 19F methods, with limitations. Quantification of iron-induced signal loss is indirect and challenging; 19F signal is directly quantifiable but lacks sensitivity. Magnetic Particle Imaging (MPI) directly detects superparamagnetic iron oxide nanoparticles (SPIO) and enables quantitation of low numbers of SPIO-labeled cells. Here we describe the first study using MPI to track and quantify the migration of DC, injected into the footpads of C57BL/6 mice, to the popliteal lymph nodes (pLNs). As DC migrate from the site of injection to the lymph nodes, we measured a decrease in signal in the footpads and an increase in signal at the pLNs. The presence of SPIO-labeled DC in nodes was validated by ex vivo MPI and histology. By measuring the iron mass per cell in samples of labeled cells, we were able to provide an estimate of cell number for each source of signal and we report a sensitivity of approximately 4000 cells in vivo and 2000 cells ex vivo. For some mice, MPI was compared to cellular MRI. We also bring attention to the issue of resolving unequal signals within close proximity, a challenge for many pre-clinical studies using a highly concentrated tracer bolus that over shadows nearby lower signals. This study demonstrates the clear advantage of MPI to detect and quantify cells in vivo, bridging the gap left by cellular MRI, and all other in vivo imaging modalities, and opening the door for quantitative imaging of cellular immunotherapies.

Sign in / Sign up

Export Citation Format

Share Document