ABSTRACT
BACKGROUND: Cell therapy is an emerging and exciting novel treatment option for cardiovascular disease that relies on the delivery of functional cells to their target site. Monitoring and tracking cells to ensure tissue delivery and engraftment is a critical step in establishing clinical and therapeutic efficacy. The study aims were (1) to develop a Good Manufacturing Practice-compliant method of labeling competent peripheral blood mononuclear cells with superparamagnetic particles of iron oxide (SPIO), and (2) to evaluate its potential for magnetic resonance cell tracking in humans. METHODS AND RESULTS: Peripheral blood mononuclear cells 1-5 × 10(9) were labeled with SPIO. SPIO-labeled cells had similar in vitro viability, migratory capacity, and pattern of cytokine release to unlabeled cells. After intramuscular administration, up to 10(8) SPIO-labeled cells were readily identifiable in vivo for at least 7 days using magnetic resonance imaging scanning. Using a phased-dosing study, we demonstrated that systemic delivery of up to 10(9) SPIO-labeled cells in humans is safe, and cells accumulating in the reticuloendothelial system were detectable on clinical magnetic resonance imaging. In a healthy volunteer model, a focus of cutaneous inflammation was induced in the thigh by intradermal injection of tuberculin. Intravenously delivered SPIO-labeled cells tracked to the inflamed skin and were detectable on magnetic resonance imaging. Prussian blue staining of skin biopsies confirmed iron-laden cells in the inflamed skin. CONCLUSIONS: Human peripheral blood mononuclear cells can be labeled with SPIO without affecting their viability or function. SPIO labeling for magnetic resonance cell tracking is a safe and feasible technique that has major potential for a range of cardiovascular applications including monitoring of cell therapies and tracking of inflammatory cells. Clinical Trial Registration- URL: http://www.clinicaltrials.gov; Unique identifier: NCT00972946, NCT01169935.
Subject(s)
Cell Tracking/methods , Contrast Media/pharmacokinetics , Dextrans/pharmacokinetics , Leukocytes, Mononuclear/metabolism , Magnetic Resonance Imaging , Cell Movement/drug effects , Contrast Media/chemistry , Cytokines/metabolism , Dextrans/chemistry , Feasibility Studies , Humans , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Magnetite Nanoparticles/chemistry , Patient Safety , Staining and Labeling , Statistics, Nonparametric , Tuberculin TestSubject(s)
Anticoagulants/adverse effects , Blood Coagulation Factors/administration & dosage , Blood Coagulation/drug effects , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Plasma , Warfarin/adverse effects , Dose-Response Relationship, Drug , Drug Therapy, Combination , Humans , International Normalized Ratio , Treatment Outcome , Vitamin K/administration & dosageABSTRACT
Palmar-plantar erythrodysaesthesia (PPE) is an uncommon cutaneous complication of cytotoxic chemotherapy which generally presents as a painful erythema involving the palms and soles. It has been suggested that PPE caused by cytarabine does not recur with subsequent cytarabine re-challenge. We report a patient with recurrent, increasingly severe episodes of PPE, ultimately complicated by a severe bullous eruption, following successive cycles of high-dose cytarabine for the treatment of acute lymphoblastic leukaemia. Contrary to previous recommendations, our experience cautions against the further use of high-dose cytarabine in patients who develop PPE, and is a timely reminder of the potential toxicity of this agent, which is now increasingly being used as first-line treatment in the management of haematologic malignancies.
