. 2015 Aug 31;88(1054):20150375. doi: 10.1259/bjr.20150375

Table 2.

Clinical trials with MRI-based cell tracking of magnetic nanoparticle-labelled cells

Study subjects	Cell type	Number of cells and route of administration	Cell labelling agent	Follow-up time with imaging	Main reported finding(s)	Publication year
Patients with melanoma	Autologous dendritic cells	7.5 × 10⁶ cells/intranodal	Ferumoxide (Endorem; Guerbet)	2 days after transplantation	MRI provided the ability to assess the accuracy of dendritic cell delivery and of internodal and intranodal cell migration patterns	2005²⁰
Patients with traumatic brain injury	Autologous neural stem cells	Cell number not specified/intracerebral around the area of brain damage	Ferumoxide^a (Feridex^®; AMAG pharmaceuticals)	24 h and every 7 days for 10 weeks after transplantation	Visualization of neural stem cell proliferation and migration from injection site to perilesional areas based on dynamic signal changes that were similar to patterns of migration observed in a subsequent study performed in rats	2006²⁸
Patients with chronic spinal cord injury patients	Autologous bone marrow-derived CD34⁺ cells	0.45–1.22 × 10⁶ cells/intrathecal into the spinal cord	CD34 monoclonal antibody-coated, micrometre-sized magnetic beads (DynalBeads^®; Dynal Biotech)	20 days and 35 days after transplantation	Visualization of hypointense signal areas at the site of injection that redistribute over time suggesting migration of the transplanted cells from the injection site to the lesion site	2007²⁹
Patients with Type 1 diabetes	Pancreatic islets	28–58 × 10⁴ pancreatic islet equivalents through multiple time-spaced injections/intraportal	Ferucarbotran (Resovist, Schering)	5 days, 6 weeks and 6 months after transplantation	Visualization of transplant-associated hypointense spots in the liver after transplantation that persisted over a period of up to 6 months. Labelling of pancreatic islets did not affect their functionality as evidenced by their retained insulin-producing capacity. Iron overload in the liver as often seen in patients with diabetes interferes with detection of labelled islets	2008²⁷
Patients with Type 1 diabetes	Pancreatic islets	7–68 × 10⁴ pancreatic islet equivalents/intraportal	Ferucarbotran (Resovist^®, Schering)	1, 4 and 24 weeks after transplantation	Visualization of pancreatic islets grafts in the liver via hypointense signal spots. Gradual decrease of the number of hypointense spot over time to 40% of original number. Sensitivity of spot detection was related to the length of labelling time of the pancreatic islets with iron oxide particles. No indications of adverse effects were found	2010²⁶
Patients with Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS)	Autologous bone marrow-derived mesenchymal stem cells	60–100 × 10⁶ cells/intrathecally and intravenously at a ratio of 2 : 1 of total dose	Ferumoxide^b (Feridex; AMAG pharmaceuticals)	4 to 48 hours and 1, 3 and 6 months after MSC infusion	MRI indicated possible dissemination of the MSCs from the lumbar site of inoculation to the occipital horns, meninges, spinal roots and spinal cord parenchyma. Observed data support the feasibility for intrathecal injection of cells for treatment of MS and ALS. No cell labelling-associated effects were observed	2010²⁴
Severe global brain ischaemic injury patient (infant)^e	Autologous cord blood-derived neural progenitors	12 × 10⁶ cells (25% labelled with iron oxide)/intraventricular in the brain	Ferumoxide^c (Endorem; Guerbet)	1 day, 1 week, and 1, 2 and 4 months after transplantation.	MRI revealed persistent (4 months) alignment of cell graft (hypointense) along lateral ventricle wall, without evidence of migration into the brain parenchyma. No cell labelling-associated adverse effects were observed.	2010²³
Healthy volunteers	Peripheral blood mononuclear cells	1–10 × 10⁸ cells/intramuscular or intravenous	Ferumoxide ^d(Endorem; Guerbet)	7 days after transplantation	MRI allowed for clear visualization of cell graft. Cell dose-dependent reduction of signal intensity in liver and spleen following intravenous cell injection, indicating dose-dependent accumulation of injected cells in these organs. Migration of labelled cells to an induced site of inflammation (performed in one volunteer). No cell labelling-associated adverse effects were observed.	2012²⁵
Patients with Type 1 diabetes	Pancreatic islets	32 × 10⁴ pancreatic islet equivalents/intraportal	Ferucarbotran (Resovist, Schering)	6 months after transplantation	Feasibility of using positive MRI techniques of iron oxide-labelled cells in a clinical setting with potentially improved transplanted cell identification capabilities.	2014²¹
Severe global brain ischaemic injury patient (infant)^e	Autologous cord blood-derived neural progenitors	12 × 10⁶ cells (25% labelled with iron oxide)/intraventricular	Ferumoxide^c(Endorem; Guerbet)	1 day, 1 week, and 1, 2, 4, 33 months after transplantation.	Total dissipation of the labelled cell-associated hypointense spots over prolonged period of time. Demonstrated in vitro feasibility of forced migration of iron-labelled cells by an external magnet.	2014²²
Patients with colorectal adenocarcinoma	Autologous dendritic cells	1–10 × 10⁶ cells/intradermal	Clinical grade perfluorocarbon nanoparticles (CS-1000, Celsense, Inc)	4 and 24 h after transplantation	Visualization of cell graft at site of injection at 4 h post transplantation with a approximately 50% reduction of signal at 24 h using a scan time of 10 minutes. No imaging evidence of migration of labelled cells was found possibly due to limited detection sensitivity. No cell labelling-associated adverse effects were observed	2014³⁹

Endoorem, Guerbet, Sulzbach, Germany; Feridex, AMAG Pharmaceuticals, Cambridge, WA; Dynal beads, Dynal Biotech, Osio, Norway; Resovist, Schering, Berlin, Germany; CS-1000, Celsense Inc., Pittsburgh, PA.

^{^a}

A non-clinical grade transfection agent (Effectene^®; Qiagen, Hilden, Germany) was used to promote cellular uptake of the iron oxide nanoparticles.

^{^b}

The transfection agent poly-l-lysine was used to promote cellular uptake of the iron oxide nanoparticles.

^{^c}

The transfection agent poly-l-lysine (Sigma, St Louis, MI) was used to promote cellular uptake of the iron oxide nanoparticles.

^{^d}

Clinical grade protamine sulphate was used as a transfection agent to promote cellular uptake of the iron oxide nanoparticles.

^{^e}

The studies by Jozwiak et al²³ from 2012 and Janowski et al²² from 2014 report on the same patient, with the article by Janowski reporting on longer follow-up of this patient and additional in vitro experiments on the labelled cells.