PITTSBURGH, PA, United States
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Balducci A.,Celsense, Inc. | Wen Y.,Duquesne University | Zhang Y.,Duquesne University | Helfer B.M.,Celsense, Inc. | And 4 more authors.
OncoImmunology | Year: 2013

A novel dual-mode contrast agent was formulated through the addition of an optical near infrared (NIR) probe to a perfluorocarbon (PFC)-based 19F magnetic resonance imaging (MRI) agent, which labels inflammatory cells in situ. A single PFC-NIR imaging agent enables both a qualitative, rapid optical monitoring of an inflammatory state and a quantitative, detailed and tissue-depth independent magnetic resonance imaging (MRI). The feasibility of in vivo optical imaging of the inflammatory response was demonstrated in a subcutaneous murine breast carcinoma model. Ex vivo optical imaging was used to quantify the PFC-NIR signal in the tumor and organs, and results correlated well with quantitative 19F NMR analyses of intact tissues. 19F MRI was employed to construct a three-dimensional image of the cellular microenvironment at the tumor site. Flow cytometry of isolated tumor cells was used to identify the cellular localization of the PFC-NIR probe within the tumor microenvironment. Contrast is achieved through the labeling of host cells involved in the immune response, but not tumor cells. The major cellular reservoir of the imaging agent were tumor-infiltrating CD11b+ F4/80low Gr-1low cells, a cell subset sharing immunophenotypic features with myeloid-derived suppressor cells (MDSC s). These cells are recruited to sites of inflammation and are implicated in immune evasion and tumor progression. This PFC-NIR contrast agent coupled to noninvasive, quantitative imaging techniques could serve as a valuable tool for evaluating novel anticancer agents. © 2013 Landes Bioscience.


Fernando Bonetto,Radboud University Nijmegen | Mangala Srinivas,Radboud University Nijmegen | Arend Heerschap,Radboud University Nijmegen | Robbie Mailliard,Celsense, Inc. | And 3 more authors.
International Journal of Cancer | Year: 2011

Monitoring of cell therapeutics in vivo is of major importance to estimate its efficacy. Here, we present a novel intracellular label for 19F magnetic resonance imaging (MRI)-based cell tracking, which allows for noninvasive, longitudinal cell tracking without the use of radioisotopes. A key advantage of 19F MRI is that it allows for absolute quantification of cell numbers directly from the MRI data. The 19F label was tested in primary human monocyte-derived dendritic cells. These cells took up label effectively, resulting in a labeling of 1.7 ± 0.1 3×10 13 19F atoms per cell, with a viability of 80 ± 6%, without the need for electroporation or transfection agents. This results in a minimum detection sensitivity of about 2,000 cells/voxel at 7 T, comparable with gadolinium-labeled cells. Comparison of the detection sensitivity of cells labeled with 19F, iron oxide and gadolinium over typical tissue background showed that unambiguous detection of the 19F-labeled cells was simpler than with the contrast agents. The effect of the 19F agent on cell function was minimal in the context of cell-based vaccines. From these data, we calculate that detection of 30,000 cells in vivo at 3 T with a reasonable signal to noise ratio for 19F images would require less than 30 min with a conventional fast spin echo sequence, given a coil similar to the one used in this study. This is well within acceptable limits for clinical studies, and thus, we conclude that 19F MRI for quantitative cell tracking in a clinical setting has great potential. © 2010 UICC.


Ahrens E.T.,University of California at San Diego | Helfer B.M.,Celsense, Inc. | O'Hanlon C.F.,Celsense, Inc. | Schirda C.,University of Pittsburgh
Magnetic Resonance in Medicine | Year: 2014

Purpose: Cellular therapeutics are emerging as a treatment option for a host of serious human diseases. To accelerate clinical translation, noninvasive imaging of cell grafts in clinical trials can potentially be used to assess the initial delivery and behavior of cells.Methods: The use of a perfluorocarbon (PFC) tracer agent for clinical fluorine-19 (19F) MRI cell detection is described. This technology was used to detect immunotherapeutic dendritic cells (DCs) delivered to colorectal adenocarcinoma patients. Autologous DC vaccines were labeled with a PFC MRI agent ex vivo. Patients received DCs intradermally, and 19F spindensity-weighted MRI at 3 Tesla (T) was used to observe cells.Results: Spin-density-weighted 19F images at the injection site displayed DCs as background-free "hot-spot" images. 19F images were acquired in clinically relevant scan times (<10 min). Apparent DC numbers could be quantified in two patients from the 19F hot-spots and were observed to decrease by ∼50% at injection site by 24 h. From 3T phantom studies, the sensitivity limit for DC detection is estimated to be on the order of ∼105 cells/voxel in this study.Conclusion: These results help to establish a clinically applicable means to track a broad range of cell types used in cell therapy. © 2014 The Authors. Magnetic Resonance in Medicine Published by Wiley Periodicals, Inc.


Patent
Celsense, Inc. | Date: 2016-02-12

Compositions and methods for assessing inflammation in a subject. The preset disclosure provides compositions for labeling leukocytes with a ^(19)F-containing perfluoropolyether molecule ex vivo. In some examples, the leukocytes are obtained from the patient, enriched in a whole blood fraction, and then labeled. The labeled cells may be re-introduced into the patient. The leukocytes may accumulate at a site of inflammation, thus permitting non-invasive evaluation of inflammation in patients. The present methods provide a tool for assessing inflammation in a wide variety of autoimmune diseases and may have particular utility in intestinal diseases such as Crohns disease, ulcerative colitis, inflammatory bowel disease, and cardio myositis.


The disclosure provides, in part, compositions and methods for producing emulsions. In certain embodiments, emulsions of the disclosure can be used for the detection of inflammation and cell tracking using MRI. The disclosure provides, in part, methods for labeling, detecting and quantifying cell members, in vivo. In certain embodiments, emulsions can be used as an artificial blood substrate.


Patent
Celsense, Inc. | Date: 2014-08-26

Compositions and methods for assessing inflammation in a subject. The present disclosure provides compositions for labeling leukocytes with a ^(19)F-containing perfluoropolyether molecule ex vivo. In some examples, the leukocytes are obtained from the patient, enriched in a whole blood fraction, and then labeled. The labeled cells may be re-introduced into the patient. The leukocytes may accumulate at a site of inflammation, thus permitting non-invasive evaluation of inflammation in patients. The present methods provide a tool for assessing inflammation in a wide variety of autoimmune diseases and may have particular utility in intestinal diseases such as Crohns disease, ulcerative colitis, inflammatory bowel disease, and cardio myositis.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 379.16K | Year: 2012

Myocardial infarction (MI) afflicts more than one million persons per year in the United States alone. MI results in permanent left ventricle (LV) scarring that causes diminished pump efficiency and, commonly, heart failure. Towards reduction or elimination of scarring, there is increasing interest in reparative biological materials, such as cells and proteins, that are introduced into the affected region of the LV early after MI. We believe that such an approach will eventually become part of a standard ofcare. The most promising route for the delivery of such materials is direct LV injection (DLVI). Thus far, the utility of DLVI has been hampered by the lack methods for accurate spatial targeting of affected tissue. This has greatly impeded clinical translation of promising materials. The goal of this project is to devise cutting edge imaging tools to visualize infarcted regions using MRI.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 169.30K | Year: 2014

DESCRIPTION (provided by applicant): Urinary incontinence (UI) is one of the most prevalent conditions, affecting approximately 40% of women in the United States and the Western world. Stress urinary incontinence (SUI) accounts for the largest portion of these women, and is found in women of all ages, including an estimated 30-40% of women above the age of 60. Despite the common surgical use of mid-urethral slings, this procedure is still associated with a disturbing level of complications. Regenerative medicine cellular therapy approaches have therefore garnered attention for treatment of SUI. In particular, the transplantation of adipose stem cells into or adjacent to the urethral sphincter muscle show promising results and appears to be a safe alternativeto traditional treatments. Efficacy of this therapy is likely dependent on both the delivery and retention of cells in the muscle but there are currently no means for assessing cellular persistence without an invasive biopsy. Celsense, Inc. focuses


Trademark
Celsense, Inc. | Date: 2012-07-24

COMPUTER SOFTWARE FOR INPUTTING, MANIPULATING AND STORING DATA REGARDING THE IN VIVO DELIVERY, MIGRATION AND PERSISTENCE OF TRANSPLANTED CELLS.

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