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Superior sensitivity of novel molecular imaging probe: simultaneously targeting two types of endothelial injury markers
Author(s) -
Sun Dawei,
Nakao Shintaro,
Xie Fang,
Zandi SouskaZandi,
Schering Alexander,
HafeziMoghadam Ali
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-148981
Subject(s) - in vivo , scanning laser ophthalmoscopy , conjugated system , adhesion , cell adhesion molecule , inflammation , fundus (uterus) , endothelium , molecular imaging , icam 1 , chemistry , microbiology and biotechnology , medicine , retinal , pathology , biophysics , biology , ophthalmology , immunology , organic chemistry , polymer
The need remains great for early diagnosis of diseases. The special structure of the eye provides a unique opportunity for noninvasive light‐based imaging of fundus vasculature. To detect endothelial injury at the early and reversible stage of adhesion molecule up‐regulation, we generated novel imaging agents that target two distinct types of endothelial molecules, a mediator of rolling, P‐selectin, and one that mediates firm adhesion, ICAM‐1. Interactions of these double‐conjugated fluorescent microspheres (MSs) in retinal or choroidal microvasculature were visualized in live animals by scanning laser ophthalmoscopy. The new imaging agents showed significantly higher sensitivity for detection of endothelial injury than singly conjugated MSs (rPSGL‐1‐ or α‐ICAM‐1‐conjugated), both in terms of rolling ( P <0.01) and firm adhesion ( P <0.01). The rolling flux of α‐ICAM‐1‐conjugated MSs did not differ in EIU animals, whereas double‐conjugated MSs showed significantly higher rolling flux ( P <0.01), revealing that ICAM‐1 in vivo supports rolling, once MS interaction with the endothelium is initiated. Double‐conjugated MSs specifically detected firmly adhering leukocytes ( P <0.01), allowing in vivo quantification of immune response. Antiinflammatory treatment with dexamethasone led to reduced leukocyte accumulation ( P <0.01) as well as MS interaction ( P <0.01), which suggests that treatment success and resolution of inflammation is quantitatively reflected with this molecular imaging approach. This work introduces novel imaging agents for noninvasive detection of endothelial injury in vivo. Our approach may be developed further to diagnose human disease at a much earlier stage than currently possible.—Sun, D., Nakao, S., Xie, F., Zandi, S., Schering, A., Hafezi‐Moghadam, A. Superior sensitivity of novel molecular imaging probe: simultaneously targeting two types of endothelial injury markers. FASEB J. 24, 1532–1540 (2010). www.fasebj.org