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

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