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A more recent version of this article appeared on November 1, 2006

Published online before print August 14, 2006
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0206110

Received for publication February 21, 2006.
Revised June 19, 2006.
Accepted for publication June 20, 2006.

Article

Quantitative magnetic resonance and SPECT imaging for macrophage tissue migration and nanoformulated drug delivery

Santhi Gorantla *{dagger}, Huanyu Dou *{dagger}, Michael Boska *{dagger}{ddagger}, Chris J. Destache {sect}, Jay Nelson *{dagger}{ddagger}, Larisa Poluektova *{dagger}, Barett E. Rabinow , Howard E. Gendelman *{dagger}@, and R. Lee Mosley *{dagger}

*Center for Neurovirology and Neurodegenerative Disorders, Departments of {dagger}Pharmacology and Experimental Neuroscience and {ddagger}Radiology, University of Nebraska Medical Center, Omaha; {sect}School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska; and Baxter Healthcare Corporation, Round Lake, Illinois

@ To whom correspondence should be addressed. E-mail: hegendel{at}unmc.edu.


  Abstract

We posit that the same mononuclear phagocytes, bone marrow (BM) and blood monocytes, tissue macrophages, microglia, and dendritic cells, which serve as targets, reservoirs, and vehicles for HIV dissemination, can be used as vehicles for antiretroviral therapy (ART). Toward this end, BM macrophages (BMM) were used as carriers for nanoparticle-formulated indinavir (NP-IDV), and the cell distribution was monitored by single photon emission computed tomography (SPECT), T2* weighted magnetic resonance imaging (MRI), histology, and {gamma}-scintillation spectrometry. BMM labeled with super paramagnetic iron oxide and/or 111indium oxine were infused i.v. into naïve mice. During the first 7 h, greater than 86% of cell label was recorded within the lungs. On Days 1, 3, 5, and 7, less than 10% of BMM were in lungs, and 74-81% and 13-18% were in liver and spleen, respectively. On a tissue-volume basis, as determined by SPECT and MRI, BMM densities in spleen and liver were significantly greater than other tissues. Migration into the lymph nodes on Days 1 and 7 accounted for 1.5-2% of the total BMM. Adoptive transfer of BMM loaded with NP-IDV produced drug levels in lymphoid and nonlymphoid tissues, which exceeded reported therapeutic concentrations by 200- to 350-fold on Day 1 and remained in excess of 100- to 300-fold on Day 14. These data show real-time kinetics and destinations of macrophage trafficking and demonstrate the feasibility of monitoring macrophage-based, nanoformulated ART.

Key Words: monocytes • cell trafficking • mouse • indinavir






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