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, R. Lee Mosley

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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 γ-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.

Original languageEnglish (US)
Pages (from-to)1165-1174
Number of pages10
JournalJournal of Leukocyte Biology
Volume80
Issue number5
DOIs
StatePublished - Nov 2006

Keywords

  • Cell trafficking
  • Indinavir
  • Monocytes
  • Mouse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Fingerprint Dive into the research topics of 'Quantitative magnetic resonance and SPECT imaging for macrophage tissue migration and nanoformulated drug delivery'. Together they form a unique fingerprint.

Cite this