Superior sensitivity of novel molecular imaging probe: Simultaneously targeting two types of endothelial injury markers

Dawei Sun, Shintaro Nakao, Fang Xie, Souska Zandi, Alexander Schering, Ali Hafezi-Moghadam

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1532-1540
Number of pages9
JournalFASEB Journal
Volume24
Issue number5
DOIs
Publication statusPublished - May 1 2010

Fingerprint

Molecular imaging
Molecular Probes
Molecular Imaging
Microspheres
Intercellular Adhesion Molecule-1
Wounds and Injuries
Imaging techniques
Adhesion
Animals
Leukocytes
Fluxes
Ophthalmoscopy
Molecules
P-Selectin
Microvessels
Dexamethasone
Endothelium
Early Diagnosis
Lasers
Anti-Inflammatory Agents

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Superior sensitivity of novel molecular imaging probe : Simultaneously targeting two types of endothelial injury markers. / Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Schering, Alexander; Hafezi-Moghadam, Ali.

In: FASEB Journal, Vol. 24, No. 5, 01.05.2010, p. 1532-1540.

Research output: Contribution to journalArticle

Sun, Dawei ; Nakao, Shintaro ; Xie, Fang ; Zandi, Souska ; Schering, Alexander ; Hafezi-Moghadam, Ali. / Superior sensitivity of novel molecular imaging probe : Simultaneously targeting two types of endothelial injury markers. In: FASEB Journal. 2010 ; Vol. 24, No. 5. pp. 1532-1540.
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