Tracking Inflammatory Cells Using Superparamagnetic Particles of Iron Oxide (SPIO) and Magnetic Resonance Imaging (MRI)

In Vivo Tracking of Magnetically-labelled Human Mononuclear Cells Using MRI Scanning

Treatment of a wide range of diseases using stem cells and other types of cell appears promising. Following administration of cells it is often not clear where exactly the cells have gone and how many of them have reached the target site. This has been one of the challenges of developing these treatment options further. We have developed a method of labelling human cells with a magnetic resonance imaging (MRI) "contrast agent" which contains tiny iron filings. Following intravenous administration it is possible to see where the iron-labelled cells have gone using MRI scanning. We would like to do is to demonstrate that these cells behave normally and migrate to a site of inflammation. We plan to induce an area of inflammation in the forearm of healthy volunteers using the Mantoux test (a test of immunity against tuberculosis) before giving the labelled cells intravenously. After the Mantoux test we will give these volunteers iron-labelled cells and do MRI scans of their forearm to determine whether these cells can be seen accumulating in the target site.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Administration of intra-dermal Endorem; Biological: Mantoux test; Biological: Autologous Endorem-labelled mononuclear cells; Drug: Administration of Endorem

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH16SU4
      • University of Edinburgh / Royal Infirmary of Edinburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male or female volunteers age 18 to 65 years
• Previous vaccine for tuberculosis more than 5 years ago

Exclusion Criteria:

• pregnancy / breast feeding
• Contra-indication to MRI scanning
• Inability or refusal to give informed consent
• Renal failure (eGFR <25mL/min) or hepatic dysfunction (Child's B or C)
• HIV/hepatitis B/hepatitis C/HTLV/syphilis
• Active malignant disease
• Anaemia
• Blood dyscrasia
• High risk of allergy to protamine sulphate (fish allergy, infertile men, vasectomy)
• Known history of tuberculosis infection.
• History of prolonged residence (> 6 months) in a region or country with a high prevalence of tuberculosis.
• Previous Mantoux reaction of 15mm of greater.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of Intra-dermal SPIO; MRI scanning before and after intra-dermal injection of SPIO.	Drug: Administration of intra-dermal Endorem; single dose, intradermal
Experimental: Mantoux, Venesection, Labelled cells; Mantoux test then MRI scanning before and after administration of iron-labelled cells obtained by venesection.	Biological: Mantoux test; single dose, intradermal; Biological: Autologous Endorem-labelled mononuclear cells; single dose, intravenous
Experimental: Mantoux, Apheresis, Labelled cells; Mantoux test then MRI scanning before and after administration of iron-labelled cells obtained by apheresis.	Biological: Mantoux test; single dose, intradermal; Biological: Autologous Endorem-labelled mononuclear cells; single dose, intravenous
Experimental: Mantoux, Administration of Endorem; Mantoux test then MRI scanning before and after administration of Endorem.	Biological: Mantoux test; single dose, intradermal; Drug: Administration of Endorem; single dose, intravenous
Experimental: Mantoux only; Mantoux test then serial MRI scanning.	Biological: Mantoux test; single dose, intradermal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in signal intensity in the region of interest on MRI scanning	0 hours, 24 hours, 48 hours, 3 - 5 days

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Collaborators: British Heart Foundation; Translational Medicine Research Collaboration
• Investigators: Principal Investigator: Jenny M Richards, MBChB MRCS, University of Edinburgh

Publications and helpful links

General Publications

• Richards JM, Shaw CA, Lang NN, Williams MC, Semple SI, MacGillivray TJ, Gray C, Crawford JH, Alam SR, Atkinson AP, Forrest EK, Bienek C, Mills NL, Burdess A, Dhaliwal K, Simpson AJ, Wallace WA, Hill AT, Roddie PH, McKillop G, Connolly TA, Feuerstein GZ, Barclay GR, Turner ML, Newby DE. In vivo mononuclear cell tracking using superparamagnetic particles of iron oxide: feasibility and safety in humans. Circ Cardiovasc Imaging. 2012 Jul;5(4):509-17. doi: 10.1161/CIRCIMAGING.112.972596. Epub 2012 Jul 10.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: July 23, 2010
• First Submitted That Met QC Criteria: July 23, 2010
• First Posted (Estimate): July 26, 2010

Study Record Updates

• Last Update Posted (Estimate): February 5, 2013
• Last Update Submitted That Met QC Criteria: February 4, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: MRI; Healthy Volunteer; SPIO
• Additional Relevant MeSH Terms: Anticoagulants; Plasma Substitutes; Blood Substitutes; Dextrans
• Other Study ID Numbers: 10/S1102/31