title: Paramagnetic nanoparticles to track and quantify in vivo immune human therapeutic cells.
abstract: This study aims to investigate gadolinium-based nanoparticles (Gd-HNP) for in vitro labeling of human plasmacytoid dendritic cells (HuPDC) to allow for in vivo tracking and HuPDC quantifying using magnetic resonance imaging (MRI) following parenteral injection. Human plasmacytoid DC were labeled (LabHuPDC) with fluorescent Gd-HNP (Gd-FITC-HNP) and injected via intraperitoneal and intravenous routes in 4-5 NOD-SCID β2m(-/-)mice (treated mice = TM). Control mice (CM) were similarly injected with unlabeled HuPDC. In vivo 7 T MRI was performed 24 h later and all spleens were removed in order to measure Gd and fluorescence contents and identify HuPDC. Gd-FITC-HNP efficiently labeled HuPDC (0.05 to 0.1 pg per cell), without altering viability and activation properties. The magnetic resonance (MR) signal was exclusively due to HuPDC. The normalized MR splenic intensity for TM was significantly higher than for CM (p < 0.024), and highly correlated with the spleen Gd content (r = 0.97), and the number of HuPDC found in the spleen (r = 0.94). Gd-FITC-HNP allowed for in vivo tracking and HuPDC quantifying by means of MRI following parenteral injection, with very high sensitivity (<3000 cells per mm(3)). The safety of these new nanoparticle types must be confirmed via extensive toxicology tests including in vivo stability and biodistribution studies.
authors.affiliation: R&D Laboratory, Etablissement Français du Sang Rhône Alpes, La Tronche, F-38701 France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Aspord
authors.forename: David
authors.initials: D
authors.lastname: Laurin
authors.forename: Marc F
authors.initials: MF
authors.lastname: Janier
authors.forename: Céline A
authors.initials: CA
authors.lastname: Mandon
authors.forename: Charles
authors.initials: C
authors.lastname: Thivolet
authors.forename: Christian
authors.initials: C
authors.lastname: Villiers
authors.forename: Pierre
authors.initials: P
authors.lastname: Mowat
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Madec
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.forename: Pascal
authors.initials: P
authors.lastname: Perriat
authors.forename: Cédric
authors.initials: C
authors.lastname: Louis
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bérard
authors.forename: Patrice N
authors.initials: PN
authors.lastname: Marche
authors.forename: Joël
authors.initials: J
authors.lastname: Plumas
authors.forename: Claire
authors.initials: C
authors.lastname: Billotey
mesh_terms: D000818:Animals; D002460:Cell Line; D058948:Cell Tracking; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D003713:Dendritic Cells / Q000737:chemistry / Q000166:cytology* / Q000637:transplantation; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry; D006801:Humans; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D058185:Magnetite Nanoparticles; D005682:Gadolinium; D016650:Fluorescein-5-isothiocyanate