Targeted imaging of human endothelial-specific marker in a model of adoptive cell transfer.
Imaging of endothelial-specific markers is critically important in non-invasive detection of early signs of vascular pathologies (eg inflammation, atherosclerosis and angiogenesis). A model of adoptive human endothelial cell (HUVEC) transfer was used to test-specific imaging probes for human vascular disease consisting of cross-linked iron oxide (CLIO) nanoparticles conjugated to anti-human E-selectin (CLIO-F(ab')(2)). To perform in vivo imaging of E-selectin expression in functional blood vessels, human vascular endothelium cells (HUVECs) were implanted in athymic mice in Matrigel solution, which served as a temporary neovascularization scaffold after the solidification. The formation of HUVEC-containing vessels was established by histology and microscopy. CLIO-F(ab')(2) probes were administered via an i.v. injection following the induction of E-selectin expression by IL-1beta. High-resolution MR images were obtained before and after the administration of CLIO-F(ab')(2), which showed specific hypointensity only if treated with IL-1beta. A three-times higher CLIO-induced MR signal decrease on T2(*) images was measured in HUVEC implants in response to IL-1beta treatment. Image signal intensity did not change in control animals that: (1) harbored Matrigel alone, (2) in the absence of IL-1beta treatment or (3) in animals injected with CLIO linked to the idiotype-matched control F(ab')(2). Experiments in an adoptive transfer model demonstrated that HUVEC-containing neovessels are perfused and that IL-1beta inducible E-selectin expression in these vessels is detectable with non-invasive imaging by using targeted nanoparticles.
Kang
Hye Won
HW
Department of Radiology, Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, USA.
Torres
Denise
D
Wald
Lawrence
L
Weissleder
Ralph
R
Bogdanov
Alexei A
AA
D019264:Adoptive Transfer; D000818:Animals; D015415:Biomarkers; D017690:Cell Transplantation; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004338:Drug Combinations; D016503:Drug Delivery Systems; D019040:E-Selectin / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology; D007797:Laminin / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures; D018919:Neovascularization, Physiologic; D011509:Proteoglycans / Q000737:chemistry; D011994:Recombinant Proteins / Q000494:pharmacology; D012996:Solutions / Q000737:chemistry; D014183:Transplantation, Heterologous; D014471:Umbilical Veins / Q000166:cytology
D015415:Biomarkers; D003432:Cross-Linking Reagents; D004338:Drug Combinations; D019040:E-Selectin; D005290:Ferric Compounds; D007140:Immunoglobulin Fab Fragments; D007375:Interleukin-1; D007797:Laminin; D011509:Proteoglycans; D011994:Recombinant Proteins; D012996:Solutions; C059485:matrigel; C000499:ferric oxide; D003094:Collagen