In vivo, multimodal imaging of B cell distribution and response to antibody immunotherapy in mice

• Published in: PloS one 2010-05, Vol.5 (5), p.e10655-e10655
• Main Authors: Thorek, Daniel L J, Tsao, Patricia Y, Arora, Vaishali, Zhou, Lanlan, Eisenberg, Robert A, Tsourkas, Andrew
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies - immunology; Autoimmune diseases; B cells; B-Lymphocytes - immunology; Bioengineering; Biotechnology; Biotechnology/Bioengineering; Brain cancer; Cells, Cultured; Contrast agents; Dendritic cells; Depletion; Disease; Drug dosages; Engineering schools; Ferric oxide; Fluorescence; Fluorescent dyes; Fluorescent indicators; House mouse; Imaging; Imaging, Three-Dimensional - methods; Immunology; Immunology/Autoimmunity; Immunology/Immunomodulation; Immunotherapy; In vivo methods and tests; Infrared tracking; Iron oxides; Labeling; Labelling; Lymphocyte Depletion; Lymphocytes; Lymphocytes B; Lymphoma; Magnetic Resonance Imaging; Medicine; Melanoma; Mice; Mice, Inbred C57BL; Microscopy; Multiple sclerosis; Nanoparticles; NMR; Non-Hodgkin's lymphoma; Nuclear magnetic resonance; Organ Specificity; Patients; Peripheral blood; Radiology and Medical Imaging; Radiology and Medical Imaging/Magnetic Resonance Imaging; Rodents; Spleen; Spleen - immunology; Spleen - pathology; Staining and Labeling; Stem cells; T cell receptors; Therapy; Tumors; Whole Body Imaging
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0010655

B cell depletion immunotherapy has been successfully employed to treat non-Hodgkin's lymphoma. In recent years, increasing attention has been directed towards also using B-cell depletion therapy as a treatment option in autoimmune disorders. However, it appears that the further development of these approaches will depend on a methodology to determine the relation of B-cell depletion to clinical response and how individual patients should be dosed. Thus far, patients have generally been followed by quantification of peripheral blood B cells, but it is not apparent that this measurement accurately reflects systemic B cell dynamics. Cellular imaging of the targeted population in vivo may provide significant insight towards effective therapy and a greater understanding of underlying disease mechanics. Superparamagnetic iron oxide (SPIO) nanoparticles in concert with near infrared (NIR) fluorescent dyes were used to label and track primary C57BL/6 B cells. Following antibody mediated B cell depletion (anti-CD79), NIR-only labeled cells were expeditiously cleared from the circulation and spleen. Interestingly, B cells labeled with both SPIO and NIR were not depleted in the spleen. Whole body fluorescent tracking of B cells enabled noninvasive, longitudinal imaging of both the distribution and subsequent depletion of B lymphocytes in the spleen. Quantification of depletion revealed a greater than 40% decrease in splenic fluorescent signal-to-background ratio in antibody treated versus control mice. These data suggest that in vivo imaging can be used to follow B cell dynamics, but that the labeling method will need to be carefully chosen. SPIO labeling for tracking purposes, generally thought to be benign, appears to interfere with B cell functions and requires further examination.