Semiquantitation of Mouse Dendritic Cell Migration In Vivo Using Cellular MRI

Summary: Despite recent therapeutic advances, including theintroduction of novel cytostatic drugs and therapeutic antibodies,many cancer patients will experience recurrent or metastaticdisease. Current treatment options, particularly for those patientswith metastatic breast, prostate, or skin cancers, are complex andhave limited curative potential. Recent clinical trials, however, haveshown that cell-based therapeutic vaccines may be used to generatebroad-based, antitumor immune responses. Dendritic cells (DC)have proved to be the most efficacious cellular component fortherapeutic vaccines, serving as both the adjuvant and antigendelivery vehicle. At present it is not possible to noninvasivelydetermine the fate of DC-based vaccines after their administrationto human subjects. In this study, we demonstrate that in vitro-generated mouse DC can be readily labeled with superparamag-netic iron oxide nanoparticles, Feridex, without altering cellmorphology, or their phenotypic and functional maturation.Feridex-labeling enables the detection of DC in vivo after theirmigration to draining lymph nodes using a 1.5T clinical magneticresonance scanner. In addition, we report a semiquantitativeapproach for analysis of magnetic resonance images and show thatthe Feridex-induced signal void volume, and fractional signal loss,correlates with the delivery and migration of small numbers of invitro-generated DC. These findings, together with ongoingpreclinical studies, are key to gaining information critical forimproving the efficacy of therapeutic vaccines for the treatmentcancer, and potentially, chronic infectious diseases.Key Words: immunotherapy, dendritic cells, vaccine, magneticresonance imaging, cancer