Endothelial targeting of polymeric nanoparticles stably labeled with the PET imaging radioisotope iodine-124.

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TitleEndothelial targeting of polymeric nanoparticles stably labeled with the PET imaging radioisotope iodine-124.
Publication TypeJournal Article
Year of Publication2012
AuthorsSimone, EA, Zern, BJ, Chacko, A-M, Mikitsh, JL, Blankemeyer, ER, Muro, S, Stan, RV, Muzykantov, VR
JournalBiomaterials
Volume33
Issue21
Pagination5406-13
Date Published2012 Jul
ISSN1878-5905
KeywordsAnimals, Antibodies, Monoclonal, Drug Delivery Systems, Endothelial Cells, Female, Iodine Radioisotopes, Lung, Mice, Mice, Inbred C57BL, Nanoparticles, Particle Size, Polyvinyls, Positron-Emission Tomography, Staining and Labeling, Time Factors
Abstract

Targeting of therapeutics or imaging agents to the endothelium has the potential to improve specificity and effectiveness of treatment for many diseases. One strategy to achieve this goal is the use of nanoparticles (NPs) targeted to the endothelium by ligands of protein determinants present on this tissue, including cell adhesion molecules, peptidases, and cell receptors. However, detachment of the radiolabel probes from NPs poses a significant problem. In this study, we devised polymeric NPs directly labeled with radioiodine isotopes including the positron emission tomography (PET) isotope (124)I, and characterized their targeting to specific endothelial determinants. This approach provided sizable, targetable probes for specific detection of endothelial surface determinants non-invasively in live animals. Direct conjugation of radiolabel to NPs allowed for stable longitudinal tracking of tissue distribution without label detachment even in an aggressive proteolytic environment. Further, this approach permits tracking of NP pharmacokinetics in real-time and non-invasive imaging of the lung in mice using micro-PET imaging. The use of this strategy will considerably improve investigation of NP interactions with target cells and PET imaging in small animals, which ultimately can aid in the optimization of targeted drug delivery.

DOI10.1016/j.biomaterials.2012.04.036
Alternate JournalBiomaterials
PubMed ID22560201
PubMed Central IDPMC3356447
Grant ListHL-087036-01A2 / HL / NHLBI NIH HHS / United States
P30 CA023108 / CA / NCI NIH HHS / United States
R01 HL083249 / HL / NHLBI NIH HHS / United States
R01 HL087036 / HL / NHLBI NIH HHS / United States
R01 HL092085 / HL / NHLBI NIH HHS / United States