Magnetic Particle Imaging: A Novel in Vivo Imaging Platform for Cancer Detection

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.

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In vivo magnetic particle imaging: angiography of inferior vena cava and aorta in rats using newly developed multicore particles

Scientific Reports ◽

10.1038/s41598-020-74151-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Azadeh Mohtashamdolatshahi ◽

Harald Kratz ◽

Olaf Kosch ◽

Ralf Hauptmann ◽

Nicola Stolzenburg ◽

...

Keyword(s):

Image Quality ◽

Inferior Vena Cava ◽

Temporal Resolution ◽

Magnetic Particle ◽

Inferior Vena ◽

Vena Cava ◽

High Temporal Resolution ◽

Magnetic Particle Imaging ◽

Particle Imaging

Abstract Magnetic Particle Imaging (MPI) is a new imaging modality, which maps the distribution of magnetic nanoparticles (MNP) in 3D with high temporal resolution. It thus may be suited for cardiovascular imaging. Its sensitivity and spatial resolution critically depend on the magnetic properties of MNP. Therefore, we used novel multicore nanoparticles (MCP 3) for in-vivo MPI in rats and analyzed dose requirements, sensitivity and detail resolution. 8 rats were examined using a preclinical MPI scanner (Bruker Biospin GmbH, Germany) equipped with a separate receive coil. MCP 3 and Resovist were administered intravenously (i.v.) into the rats’ tail veins at doses of 0.1, 0.05 and 0.025 mmol Fe/kg followed by serial MPI acquisition with a temporal resolution of 46 volumes per second. Based on a qualitative visual scoring system MCP 3–MPI images showed a significantly (P ≤ 0.05) higher image quality than Resovist-MPI images. Morphological features such as vessel lumen diameters (DL) of the inferior vena cava (IVC) and abdominal aorta (AA) could be assessed along a 2-cm segment in mesenteric area only after administration of MCP 3 at dosages of 0.1, 0.05 mmol Fe/kg. The mean DL ± SD estimated was 2.7 ± 0.6 mm for IVC and 2.4 ± 0.7 mm for AA. Evaluation of DL of the IVC and AA was not possible in Resovist-MPI images. Our results show, that MCP 3 provide better image quality at a lower dosage than Resovist. MCP 3-MPI with a clinically acceptable dose of 0.05 mmol Fe/kg increased the visibility of vessel lumens compared to Resovist-based MPI towards possible detection of vascular abnormalities such as stenosis or aneurysms, in vivo.

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In vivo tracking and quantification of inhaled aerosol using magnetic particle imaging towards inhaled therapeutic monitoring

Theranostics ◽

10.7150/thno.26608 ◽

2018 ◽

Vol 8 (13) ◽

pp. 3676-3687 ◽

Cited By ~ 27

Author(s):

Zhi Wei Tay ◽

Prashant Chandrasekharan ◽

Xinyi Yedda Zhou ◽

Elaine Yu ◽

Bo Zheng ◽

...

Keyword(s):

Magnetic Particle ◽

Therapeutic Monitoring ◽

Magnetic Particle Imaging ◽

Particle Imaging

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Combined in vivo magnetic particle imaging and in vivo magnetic resonance imaging in mouse

2015 5th International Workshop on Magnetic Particle Imaging (IWMPI) ◽

10.1109/iwmpi.2015.7107028 ◽

2015 ◽

Author(s):

M. G. Kaul ◽

H. Ittrich ◽

O. Weber ◽

U. Heinen ◽

A. Reitmeier ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Magnetic Particle ◽

Resonance Imaging ◽

Magnetic Particle Imaging ◽

Particle Imaging

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Tracking Adoptive T Cell Therapy Using Magnetic Particle Imaging

10.1101/2020.06.02.128587 ◽

2020 ◽

Cited By ~ 2

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.

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Abstract 2770: Imaging cancer immunology: Monitoring CD47 mAb treatment in vivo by magnetic particle imaging

10.1158/1538-7445.am2020-2770 ◽

2020 ◽

Author(s):

Gang Ren ◽

Jeff M. Gaudet ◽

Marco Gerosa ◽

Yanrong Zhang ◽

James Mansfield ◽

...

Keyword(s):

Magnetic Particle ◽

Cancer Immunology ◽

Magnetic Particle Imaging ◽

Particle Imaging

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Magnetic Particle Imaging-Guided Heating in Vivo Using Gradient Fields for Arbitrary Localization of Magnetic Hyperthermia Therapy

ACS Nano ◽

10.1021/acsnano.8b00893 ◽

2018 ◽

Vol 12 (4) ◽

pp. 3699-3713 ◽

Cited By ~ 97

Author(s):

Zhi Wei Tay ◽

Prashant Chandrasekharan ◽

Andreina Chiu-Lam ◽

Daniel W. Hensley ◽

Rohan Dhavalikar ◽

...

Keyword(s):

Magnetic Particle ◽

Magnetic Hyperthermia ◽

Magnetic Particle Imaging ◽

Hyperthermia Therapy ◽

Gradient Fields ◽

Particle Imaging

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In vivo multimodal magnetic particle imaging (MPI) with tailored magneto/optical contrast agents

Biomaterials ◽

10.1016/j.biomaterials.2015.02.040 ◽

2015 ◽

Vol 52 ◽

pp. 251-261 ◽

Cited By ~ 52

Author(s):

Hamed Arami ◽

Amit P. Khandhar ◽

Asahi Tomitaka ◽

Elaine Yu ◽

Patrick W. Goodwill ◽

...

Keyword(s):

Contrast Agents ◽

Magnetic Particle ◽

Optical Contrast ◽

Optical Contrast Agents ◽

Magnetic Particle Imaging ◽

Particle Imaging

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

10.1101/2020.07.12.197780 ◽

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.

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