Tracking Peripheral Blood Mononuclear Cells With Fluorine MRI

2016-10-03 23:38:21 | BioPortfolio


Cell-based therapies in the form of stem cell-based or immune cell-based therapies are becoming important treatment options that are either approved for clinical use or are showing promise in clinical trials. One of the issues regarding cell-based therapies is that, once the cells are injected into a subject, there is no easy way to track where they go, assess whether adequate numbers of cells arrive at the intended therapeutic target and for how long they persist at a given location. To address this issue non-invasive imaging methods have been developed using magnetic resonance imaging (MRI). When used with an appropriate cell labelling contrast agent, Cellular MRI can track cells non-invasively in vivo. Detection of cells is accomplished with an inert imaging agent containing the MRI sensitive fluorine-19 (19F) nuclei. The objective of this study is to demonstrate that 19F-MRI is safe to use in humans so that it can subsequently be used to track cell-based immunotherapies in future clinical trials. The long term goal is to be able to quantify immune cell migration to secondary lymphoid tissues and potentially to tumors and correlate to therapeutic outcomes.


Background: None of the currently available Good Manufacturing Practices (GMP)-grade MRI cell labelling agents are approved for use in Canada. There is one iron oxide nanoparticle GMP grade preparation that is commercially available but it is not suitable for labelling the immune cell populations the investigators are interested in tracking in vivo. The investigators have, instead, chosen to develop the commercially available, GMP-grade 19F-based perfluorocarbon, known as Cell Sense, for the purpose of tracking immune cell-based vaccine therapies in vivo. This agent has been successful used in a phase I clinical trial in United States and is approved for a second trial current recruiting, under the oversight of the FDA.

The cell tracing agent Cell Sense (CS-1000) is an inert, non-metabolizable tracer. As CS-1000 is taken-up and incorporated into the cell traditional pharmacodynamic and pharmacokinetic analyses in animals and humans are not appropriate, as adsorption and biodistribution will vary with cell type, and therefore have not been done. In vitro studies of toxicity towards various cell types did not yield evidence of adverse effects on various cell functions. Cell Sense also was shown to be non-mutagenic using the Ames and Forward thymidine kinase (TK) assays. Some limited skin irritation was observed when >2,500 fold more Cell Sense than expected to be maximally injected into humans was injected intradermally into rats.

Examples of MRI cell tracking labels include superparamagnetic iron oxide nanoparticles and 19F-containing compounds such as perfluorocarbons. The advantage of using cellular MRI to track cells is that a non-radioactive tracer is used that is suitable for longitudinal studies. MRI offers 3D imaging with exquisite soft tissue contrast. The additional advantage of using 19F over iron-based agents is that 19F is a positive, easily quantifiable contrast cell labelling agent. Furthermore, there is no 19F-background MRI signal in humans whereas MRI involving iron can be confounded by different imaging artifacts and it is a negative contrast agent that is difficult to accurately quantify. The investigators are particularly interested in whether immune cells arrive in secondary lymphoid organs such as lymph nodes.

Study Design:

Open label, dose escalating, single centre, phase I study that will accrue (a) 6 healthy adults and (b) 6 prostate cancer patients.

Three healthy adults and three prostate cancer patients will be enrolled into the first cohort. Whole blood (150 ml) will be obtained by venipuncture. After processing of the blood to obtain peripheral blood mononuclear cells (PBMC), half of the PBMC will be treated with Cell Sense for 8-24 hours. Given the robustness of our data using 5 donors during dry runs, the investigators do not propose to compare labeled vs unlabeled cells as release criteria. However, the investigators will be collecting this data for information and research purposes. Three million (3 x 106) Cell Sense labeled autologous PBMC will be administered intradermally to the cohort 1 subjects. The three healthy adults and the 3 prostate cancer subjects will be tested concurrently.

If no grade 2 or higher adverse events are observed with the 1st cohort, concurrent enrolment will proceed to recruit a second set of 3 healthy adult subjects and the second set of 3 prostate cancer patients. The second cohort of subjects will be subjected to the same design but with an escalation of the dose to 2-3 x 107 Cell Sense-labeled autologous PBMC administered intradermally.


Primary Endpoints:

Determine the feasibility of using Cell Sense to detect and monitor the migration of PBMC in humans

Secondary Endpoints:

- Confirm and further optimize the 19F Cell Sense detection and Hydrogen- 1 (1H) anatomical imaging parameters for imaging using the 19F/1H dual coil.

- Determine if Cell Sense-labeled PBMC migration to the draining lymph node can be detected.

- Determine if the lymph nodes in the area of interest imaged change in size on the injected side compared to the contralateral side.

- Quantify the number of Cell Sense-labeled PBMC detected.

- Evaluate safety parameters (toxicity) as defined by:

- adverse events.

- serious adverse events.

- changes in laboratory determination and vital sign parameters as assessed by medical history, physical examination and clinical laboratory tests.

The following categories will be used to grade any adverse events:

- Grade 1: does not interfere with daily activity,

- Grade 2: interferes with daily activity, no treatment required, except paracetamol,

- Grade 3: prevents daily activity or requires treatment.

- Grade 4: Life-threatening

NIH and FDA (or CTCAE v 4.0) guidelines will be used to determine the severity of adverse events

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Basic Science


Adverse Reaction to Diagnostic Agents and Kits Nos


19F Cell Sense-labeled PBMC, MRI


Robarts Research Institute
N6A 5B7


Not yet recruiting


Western University, Canada

Results (where available)

View Results


Published on BioPortfolio: 2016-10-03T23:38:21-0400

Clinical Trials [1516 Associated Clinical Trials listed on BioPortfolio]

99m-Tc Labeled Anti-PD-L1 VHH for Diagnostic Imaging of Non-Small Cell Lung Cancer

To evaluate the efficacy and safety of 99m-Tc labeled anti-PD-L1 VHH for SPECT/CT diagnostic imaging of Non-Small Cell Lung Cancer and compare it with the existing gold standard "biopsy PD...

Pivotal Study of the Al-Sense Study Protocol

The purpose of this study is to demonstrate that the Diagnostic Absorbent Panty liner (AL-SENSE Amniotic Leak Test Kit), developed by Common Sense Ltd., can distinguish between wetness sen...

Special Investigation For Renal Cell Carcinoma (RCC) Of Sunitinib Malate (Regulatory Post Marketing Commitment Plan)

The objective of this surveillance is to collect information about 1) adverse drug reaction not expected from the LPD (unknown adverse drug reaction), 2) the incidence of adverse drug reac...

Safety and Efficacy of Xalkori ROS1

The objective of this surveillance is to collect information about 1) adverse drug reaction not expected from the LPD (unknown adverse drug reaction), 2) the incidence of adverse drug reac...

Safety And Efficacy Of Crizotinib (Regulatory Post Marketing Commitment Plan)

The objective of this surveillance is to collect information about 1) adverse drug reaction not expected from the LPD (unknown adverse drug reaction), 2) the incidence of adverse drug reac...

PubMed Articles [31278 Associated PubMed Articles listed on BioPortfolio]

Anti-Sense Antibiotic Agents as Treatment for Bacterial Infections.

Conventional antibiotic agents are overused, leading to decreased efficacy because of a rising incidence in antimicrobial resistance. Further, conventional antibiotic agents result in widespread effec...

The rational specimen for the quantitative detection of Epstein-Barr virus DNA load.

Background Epstein-Barr virus (EBV) DNA load monitoring in blood is essential for the diagnosis of EBV-associated diseases. However, the best-suited blood compartment for detection is still under disc...

In vitro analysis of antigen induced T cell-monocyte conjugates by imaging flow cytometry.

There is a lack of suitable correlates of immune protection against Mycobacterium tuberculosis (Mtb) infection. T cells and monocytes play key roles in host immunity against Mtb. Thus, a method that a...

Quantitation of intracellular triphosphate metabolites of antiretroviral agents in peripheral blood mononuclear cells (pbmcs) and corresponding cell count determinations: review of current methods and challenges.

PBMCs are a critical component of the immune system and the target cells for HIV-1 infection. Nucleoside/nucleotide analogs for the treatment of HIV infection are prodrugs that require cellular activa...

Coordination-Mediated Synthesis of Ga-Labeled Purification-Free Trivalent Probes for In Vivo Imaging of Saturable Systems.

A large excess of unlabeled ligands over gallium-67 (Ga) provide Ga-labeled probes with high radiochemical yields in short reaction time. However, the unlabeled ligand hinders target accumulation of r...

Medical and Biotech [MESH] Definitions

Systems developed for collecting reports from government agencies, manufacturers, hospitals, physicians, and other sources on adverse drug reactions.

Organisms, biological agents, or biologically-derived agents used strategically for their positive or adverse effect on the physiology and/or reproductive health of other organisms.

Adverse reactions that occur initially at the site of injection or infusion. Milder type is confined to a local allergic flare reaction. A more severe reaction is caused by extravasation of VESICANTS from the blood vessel at the site of injection and can cause damage to the surrounding tissue. In tumor flare reaction symptoms involve well beyond the injection site such as an increase in the tumor size and tumor markers levels, bone pain, and HYPERCALCEMIA.

An electrophoretic technique for assaying the binding of one compound to another. Typically one compound is labeled to follow its mobility during electrophoresis. If the labeled compound is bound by the other compound, then the mobility of the labeled compound through the electrophoretic medium will be retarded.

Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available.

More From BioPortfolio on "Tracking Peripheral Blood Mononuclear Cells With Fluorine MRI"

Quick Search


Relevant Topics

Stem Cells
Track and monitor developments in stem cell research and commercial development.  Follow the tabs above to read the latest global news, research, clinical trials on stem cells and follow companies active in the stem cell industry.  BioPort...

Clinical Approvals
Clinical trials are a set of procedures in medical research conducted to allow safety (or more specifically, information about adverse drug reactions and adverse effects of other treatments) and efficacy data to be collected for health interventions (e.g...

Searches Linking to this Trial