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Published online before print August 14, 2006

This Article Full Text Full Text (PDF) Supplemental data: jlb.0206110 All Versions of this Article: jlb.0206110v1 80/5/1165    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gorantla, S. Articles by Mosley, R. L. Search for Related Content PubMed PubMed Citation Articles by Gorantla, S. Articles by Mosley, R. L.

(Journal of Leukocyte Biology. 2006;80:1165-1174.)
© 2006 by Society for Leukocyte Biology

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

Santhi Gorantla^*,, Huanyu Dou^*,, Michael Boska^*,,, Chris J. Destache, Jay Nelson^*,,, Larisa Poluektova^*,, Barett E. Rabinow^¶, Howard E. Gendelman^*,,1 and R. Lee Mosley^*,

^* Center for Neurovirology and Neurodegenerative Disorders, Departments of
Pharmacology and Experimental Neuroscience and
Radiology, University of Nebraska Medical Center, Omaha, Nebraska, USA;
School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska, USA; and
^¶ Baxter Healthcare Corporation, Round Lake, Illinois, USA

¹ Correspondence: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880. E-mail: hegendel{at}unmc.edu

ABSTRACT

We posit that the same mononuclear phagocytes (MP) [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), transverse relation time (T₂)* weighted magnetic resonance imaging (MRI), histology, and -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 that 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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