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Updated: Aug 6, 2026
Registered Bioimaging of Nanomaterials for Diagnostic and Therapeutic Monitoring
Published on: December 9, 2010
Quantitative magnetic resonance and SPECT imaging for macrophage tissue migration and nanoformulated drug delivery
Santhi Gorantla1, Huanyu Dou, Michael Boska
1Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA.
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 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 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.
Insights
Mononuclear phagocytes can deliver antiretroviral therapy (ART). Bone marrow macrophages loaded with nanoparticle-indinavir showed high drug levels in tissues, demonstrating feasibility for macrophage-based ART delivery.
Area of Science:
- Immunology
- Nanomedicine
- Pharmacology
Background:
- Mononuclear phagocytes (MP) are key in HIV dissemination.
- MP can potentially be utilized for targeted drug delivery.
Purpose of the Study:
- To investigate the use of bone marrow macrophages (BMM) as carriers for nanoparticle-formulated antiretroviral therapy (ART).
- To monitor the distribution and trafficking of BMM using advanced imaging techniques.
- To assess the therapeutic drug levels achieved by BMM-based ART delivery.
Main Methods:
- BMM were loaded with nanoparticle-indinavir (NP-IDV).
- Cell distribution was tracked using SPECT, MRI, histology, and gamma-scintillation spectrometry in mice.
- Drug concentrations in lymphoid and non-lymphoid tissues were measured.
Main Results:
- BMM primarily localized in the lungs initially, then shifted to the liver and spleen.
- SPECT and MRI confirmed higher BMM density in spleen and liver.
- BMM-based ART achieved drug levels 200-350 fold above therapeutic concentrations on Day 1, sustained through Day 14.
Conclusions:
- Bone marrow macrophages can be effectively tracked in vivo.
- Macrophage-based delivery of nanoformulated ART is feasible and achieves high therapeutic drug levels.
- This approach offers a potential new strategy for HIV treatment.
