title: Semiquantitation of mouse dendritic cell migration in vivo using cellular MRI.
abstract: Despite recent therapeutic advances, including the introduction of novel cytostatic drugs and therapeutic antibodies, many cancer patients will experience recurrent or metastatic disease. Current treatment options, particularly for those patients with metastatic breast, prostate, or skin cancers, are complex and have limited curative potential. Recent clinical trials, however, have shown that cell-based therapeutic vaccines may be used to generate broad-based, antitumor immune responses. Dendritic cells (DC) have proved to be the most efficacious cellular component for therapeutic vaccines, serving as both the adjuvant and antigen delivery vehicle. At present it is not possible to noninvasively determine the fate of DC-based vaccines after their administration to human subjects. In this study, we demonstrate that in vitro-generated mouse DC can be readily labeled with superparamagnetic iron oxide nanoparticles, Feridex, without altering cell morphology, or their phenotypic and functional maturation. Feridex-labeling enables the detection of DC in vivo after their migration to draining lymph nodes using a 1.5 T clinical magnetic resonance scanner. In addition, we report a semiquantitative approach for analysis of magnetic resonance images and show that the Feridex-induced signal void volume, and fractional signal loss, correlates with the delivery and migration of small numbers of in vitro-generated DC. These findings, together with ongoing preclinical studies, are key to gaining information critical for improving the efficacy of therapeutic vaccines for the treatment cancer, and potentially, chronic infectious diseases.
authors.affiliation: Biotherapeutics Research Group, University of Western Ontario, London, Ontario, Canada.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Dekaban
authors.forename: Jonatan
authors.initials: J
authors.lastname: Snir
authors.forename: Bradly
authors.initials: B
authors.lastname: Shrum
authors.forename: Sonali
authors.initials: S
authors.lastname: de Chickera
authors.forename: Christy
authors.initials: C
authors.lastname: Willert
authors.forename: Mia
authors.initials: M
authors.lastname: Merrill
authors.forename: Elias A
authors.initials: EA
authors.lastname: Said
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sekaly
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Foster
authors.forename: Peta J
authors.initials: PJ
authors.lastname: O'Connell
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003287:Contrast Media / Q000737:chemistry; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007501:Iron / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D008810:Mice, Inbred C57BL; D010087:Oxides / Q000737:chemistry
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide