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.

scholarly journals IMMU-25. MAGNETIC PARTICLE IMAGING FOR NON-INVASIVE TRACKING OF ADOPTIVE CELL TRANSFER IN CANCER IMMUNOTHERAPY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi124-vi124
Author(s):  
Angelie Rivera-Rodriguez ◽  
Lan Hoang-Minh ◽  
Leyda Marrero-Morales ◽  
Duane Mitchell ◽  
Carlos Rinaldi
Keyword(s):  
T Cells ◽  
Ex Vivo ◽  
Cell Transfer ◽  
Cell Therapies ◽  
Non Invasive ◽  
Magnetic Particle Imaging ◽  
Particle Imaging ◽  
T Cell Transfer ◽  
Cytotoxic Function

Abstract BACKGROUND Adoptive cell therapies (ACT) are strategies being explored to boost the immune response against cancer. ACT cancer immunotherapies are effective against metastatic melanoma, leukemia, and lymphoma, but face challenges in treating other solid tumors, such as in the brain. A critical step for the success of ACT in solid cancers is achieving trafficking and persistence of T-cells at tumor sites. Glioblastoma (GBM) is the most common and aggressive cancer of the central nervous system in adults, with a prognosis of 15-18-month average patient survival after diagnosis. Biomedical imaging is often used to track cell therapies. Magnetic Particle Imaging (MPI) is a novel biomedical imaging modality enabling non-invasive visualization of the distribution of biocompatible superparamagnetic iron oxide (SPIO) tracers. OBJECTIVE Label T-cells with SPIO to non-invasively track adoptive T cell transfer immunotherapy with MPI in the context of brain cancer. METHODS Murine pmel-DsRed T-cells were isolated from the spleen of a transgenic C57BL/6 mouse, and were exposed to different SPIO concentrations ex vivo. Cell viability, phenotype, and cytotoxic function were analyzed to determine if T-cells were affected by the SPIO labeling. Moreover, in vivo experiments were performed in a murine GBM model, and labeled T-cells were injected intravenously and tracked using MPI. RESULTS The SPIO-labeling of T-cells did not affected cell viability, phenotype, or cell cytotoxic function at all tested incubation conditions. The internalized SPIO can be quantified and spatially detected using MPI both in vitro and in vivo. In addition, MPI in vivo tracking shows T-cells accumulation in liver and lungs, as well in the spleen and brain, as showed ex vivo. CONCLUSIONS SPIO-labeling of T-cells did not affected its cytotoxic function and MPI allows for in vivo tracking of adoptively T-cell transfer. MPI will provide better understanding of ACT dynamics to accelerate development of novel treatments.

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.

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 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 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.

scholarly journals Adoptive Cellular Therapy for Solid Tumors

2021 ◽  
pp. 57-65
Author(s):  
Adham S. Bear ◽  
Joseph A. Fraietta ◽  
Vivek K. Narayan ◽  
Mark O’Hara ◽  
Naomi B. Haas
Keyword(s):  
T Cells ◽  
T Cell ◽  
Solid Tumors ◽  
Gene Editing ◽  
Cellular Therapy ◽  
Immune Cell ◽  
Ex Vivo ◽  
Oncolytic Viruses ◽  
Adoptive Cellular Therapy

Cancer immunotherapy tools include antibodies, vaccines, cytokines, oncolytic viruses, bispecific molecules, and cellular therapies. This review will focus on adoptive cellular therapy, which involves the isolation of a patient’s own immune cells followed by their ex vivo expansion and reinfusion. The majority of adoptive cellular therapy strategies utilize T cells isolated from tumor or peripheral blood, but may utilize other immune cell subsets. T-cell therapies in the form of tumor-infiltrating lymphocytes, T-cell receptor T cells, and CAR T cells may act as “living drugs” as these infused cells expand, engraft, and persist in vivo, allowing adaptability over time and enabling durable remissions in subsets of patients. Adoptive cellular therapy has been less successful in the management of solid tumors because of poor homing, proliferation, and survival of transferred cells. Strategies are discussed, including expression of transgenes to address these hurdles. Additionally, advances in gene editing using CRISPR/Cas9 and similar technologies are described, which allow for clinically translatable gene-editing strategies to enhance the antitumor activity and to surmount the hostilities advanced by the host and the tumor. Finally, the common toxicities and approaches to mitigate these are reviewed.

scholarly journals 413 GEN-009, a personalized neoantigen vaccine, elicits robust immune responses in individuals with advanced or metastatic solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A438-A438
Author(s):  
Mara Shainheit ◽  
Devin Champagne ◽  
Gabriella Santone ◽  
Syukri Shukor ◽  
Ece Bicak ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Solid Tumors ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Checkpoint Blockade ◽  
T Cell Subsets ◽  
Cell Responses

BackgroundATLASTM is a cell-based bioassay that utilizes a cancer patient‘s own monocyte-derived dendritic cells and CD4+ and CD8+ T cells to screen their mutanome and identify neoantigens that elicit robust anti-tumor T cell responses, as well as, deleterious InhibigensTM.1 GEN-009, a personalized vaccine comprised of 4–20 ATLAS-identified neoantigens combined with Hiltonol®, harnesses the power of neoantigen-specific T cells to treat individuals with solid tumors. The safety and efficacy of GEN-009 is being assessed in a phase 1/2a clinical trial (NCT03633110).MethodsA cohort of 15 adults with solid tumors were enrolled in the study. During the screening period, patients received standard of care PD-1-based immunotherapies appropriate for their tumor type. Subsequently, patients were immunized with GEN-009 with additional doses administered at 3, 6, 12, and 24 weeks. Peripheral blood mononuclear cells (PBMCs) were collected at baseline, pre-vaccination (D1), as well as 29, 50, 92, and 176 days post first dose. Vaccine-induced immunogenicity and persistence were assessed by quantifying neoantigen-specific T cell responses in ex vivo and in vitro stimulation dual-analyte fluorospot assays. Polyfunctionality of neoantigen-specific T cells was evaluated by intracellular cytokine staining. Additionally, potential correlations between the ATLAS-identified profile and vaccine-induced immunogenicity were assessed.ResultsGEN-009 augmented T cell responses in 100% of evaluated patients, attributable to vaccine and not checkpoint blockade. Furthermore, neoantigen-induced secretion of IFNγ and/or TNFα by PBMCs, CD4+, and CD8+ T cells was observed in all patients. Responses were primarily from polyfunctional TEM cells and detectable in both CD4+ and CD8+ T cell subsets. Some patients had evidence of epitope spreading. Unique response patterns were observed for each patient with no apparent relationship between tumor types and time to emergence, magnitude or persistence of response. Ex vivo vaccine-induced immune responses were observed as early as 1 month, and in some cases, persisted for 176 days. Clinical efficacy possibly attributable to GEN-009 was observed in several patients, but no correlation has yet been identified with neoantigen number or magnitude of immune response.ConclusionsATLAS empirically identifies stimulatory neoantigens using the patient‘s own immune cells. GEN-009, which is comprised of personalized, ATLAS-identified neoantigens, elicits early, long-lasting and polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses in individuals with advanced cancer. Several patients achieved clinical responses that were possibly attributable to vaccine; efforts are underway to explore T cell correlates of protection. These data support that GEN-009, in combination with checkpoint blockade, represents a unique approach to treat solid tumors.AcknowledgementsWe are grateful to the patients and their families who consented to participate in the GEN-009-101 clinical trial.Trial RegistrationNCT03633110Ethics ApprovalThis study was approved by Western Institutional Review Board, approval number 1-1078861-1. All subjects contributing samples provided signed individual informed consent.ReferenceDeVault V, Starobinets H, Adhikari S, Singh S, Rinaldi S, Classon B, Flechtner J, Lam H. Inhibigens, personal neoantigens that drive suppressive T cell responses, abrogate protection of therapeutic anti-tumor vaccines. J. Immunol 2020; 204(1 Supplement):91.15.

scholarly journals IMMU-31. QUANTITATIVE EVALUATION OF ROUTES OF ADMINISTRATION OF IMMUNOTHERAPEUTIC T CELLS TO ORTHOTOPIC GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii111-ii111
Author(s):  
Lan Hoang-Minh ◽  
Angelie Rivera-Rodriguez ◽  
Fernanda Pohl-Guimarães ◽  
Seth Currlin ◽  
Christina Von Roemeling ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Ex Vivo ◽  
Adoptive T Cell Therapy ◽  
Whole Body ◽  
T Cell Therapy ◽  
Clinical Responses

Abstract SIGNIFICANCE Adoptive T cell therapy (ACT) has emerged as the most effective treatment against advanced malignant melanoma, eliciting remarkable objective clinical responses in up to 75% of patients with refractory metastatic disease, including within the central nervous system. Immunologic surrogate endpoints correlating with treatment outcome have been identified in these patients, with clinical responses being dependent on the migration of transferred T cells to sites of tumor growth. OBJECTIVE We investigated the biodistribution of intravenously or intraventricularly administered T cells in a murine model of glioblastoma at whole body, organ, and cellular levels. METHODS gp100-specific T cells were isolated from the spleens of pmel DsRed transgenic C57BL/6 mice and injected intravenously or intraventricularly, after in vitro expansion and activation, in murine KR158B-Luc-gp100 glioma-bearing mice. To determine transferred T cell spatial distribution, the brain, lymph nodes, heart, lungs, spleen, liver, and kidneys of mice were processed for 3D imaging using light-sheet and multiphoton imaging. ACT T cell quantification in various organs was performed ex vivo using flow cytometry, 2D optical imaging (IVIS), and magnetic particle imaging (MPI) after ferucarbotran nanoparticle transfection of T cells. T cell biodistribution was also assessed in vivo using MPI. RESULTS Following T cell intravenous injection, the spleen, liver, and lungs accounted for more than 90% of transferred T cells; the proportion of DsRed T cells in the brains was found to be very low, hovering below 1%. In contrast, most ACT T cells persisted in the tumor-bearing brains following intraventricular injections. ACT T cells mostly concentrated at the periphery of tumor masses and in proximity to blood vessels. CONCLUSIONS The success of ACT immunotherapy for brain tumors requires optimization of delivery route, dosing regimen, and enhancement of tumor-specific lymphocyte trafficking and effector functions to achieve maximal penetration and persistence at sites of invasive tumor growth.

scholarly journals IMMU-28. INDUCTION OF TERTIARY LYMPHOID STRUCTURE-LIKE T-CELL CLUSTERS BY DELIVERY OF A NOVEL GENE COMBINATION INTO AN IMMUNOCOMPETENT MOUSE MODEL OF GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii110-ii111
Author(s):  
Kira Downey ◽  
Bindu Hegde ◽  
Zinal Chheda ◽  
Jason Zhang ◽  
Hideho Okada
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymphatic Drainage ◽  
Lymphoid Follicle ◽  
Brain Parenchyma ◽  
Cell Therapies ◽  
Gene Combination ◽  
Cell Clustering ◽  
The Brain

Abstract The lack of conventional lymphatic drainage to and from the brain parenchyma restricts the capacity of the peripheral immune system to recognize and respond to glioma antigens. In some peripheral solid tumor types and central nervous system autoimmunity, the spontaneous development of tertiary lymphoid structures (TLS) with varying degrees of organization have been observed in human patients and mice following chronic inflammation. In the cancer setting, presence of TLS are generally associated with improved prognosis, especially when they are characterized by intratumoral infiltration of CD8+ T-cells. We aimed to induce the development of TLS in vivo, utilizing our SB28 glioblastoma model which is sparsely infiltrated by lymphocytes. As a proof-of-concept study, we stably transduced SB28 with a combination of several TLS-stimulating factors that we’ve identified and injected these cells into the brain parenchyma of syngeneic C57BL/6J mice. A combination of the chemoattractant and lymphoid follicle-stimulating cytokines LIGHT, CCL21, IL-7, and IL-17 produced substantial infiltration of CD8+CD3+ T-cells into the tumor and nearby parenchyma. However, this combination was also associated with accelerated tumor growth. A modified gene combination including LIGHT, CCL21, and IL-7 promoted CD8+CD3+ T-cell infiltration by flow cytometry, T-cell clustering by immunofluorescence analysis, and inhibited tumor burden compared with the control as measured by bioluminescent imaging. There was also evidence of increased lymphatic vasculature around the margins of T-cell clustering as demonstrated by LYVE-1 staining. Together, these analyses highlight a role for these factors in stimulating the recruitment and clustering of T-cell to the glioblastoma microenvironment in a TLS-like phenomenon. Future studies will evaluate whether the recruitment of other lymphocytes and stromal cells to these TLS-like clusters can promote T-cell memory and persistence. Ultimately, we aim to provide these factors utilizing a gene delivery method that will prove translatable to the clinic and complementary to existing T-cell therapies.

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

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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