Abstract:
BACKGROUND:The alpha(v)beta3 integrin plays a critical role in cell proliferation and migration. We hypothesized that vascular cell proliferation, a hallmark of injury-induced remodeling, can be tracked by targeting alpha(v)beta3 integrin expression in vivo. METHODS AND RESULTS:RP748, a novel 111In-labeled alpha(v)beta3-specific radiotracer, was evaluated for its cell-binding characteristics and ability to track injury-induced vascular proliferation in vivo. Three groups of experiments were performed. In cultured endothelial cells (ECs), TA145, a cy3-labeled homologue of RP748, localized to alpha(v)beta3 at focal contacts. Activation of alpha(v)beta3 by Mn2+ led to increased EC binding of TA145. Left common carotid artery wire injury in apolipoprotein E-/- mice led to vascular wall expansion over a period of 4 weeks. RP748 (7.4 MBq) was injected into groups of 9 mice at 1, 3, or 4 weeks after left carotid injury, and carotids were harvested for autoradiography. Relative autographic intensity, defined as counts/pixel of the injured left carotid area divided by counts/pixel of the uninjured right carotid area, was higher at 1 and 3 weeks (1.8+/-0.1 and 1.9+/-0.2, respectively) and decreased significantly by 4 weeks after injury (1.4+/-0.1, P<0.05). Carotid alpha(v) and beta3 integrin expression was maximal at 1 week and decreased by 4 weeks after injury. The proliferation index, as determined by Ki67 staining, followed a temporal pattern similar to that of RP748 uptake. Dynamic gamma imaging demonstrated rapid renal clearance of RP748. CONCLUSIONS:RP748 has preferential binding to activated alpha(v)beta3 integrin and can track the injury-induced vascular proliferative process in vivo.
journal_name
Circulationjournal_title
Circulationauthors
Sadeghi MM,Krassilnikova S,Zhang J,Gharaei AA,Fassaei HR,Esmailzadeh L,Kooshkabadi A,Edwards S,Yalamanchili P,Harris TD,Sinusas AJ,Zaret BL,Bender JRdoi
10.1161/01.CIR.0000133319.84326.70subject
Has Abstractpub_date
2004-07-06 00:00:00pages
84-90issue
1eissn
0009-7322issn
1524-4539pii
01.CIR.0000133319.84326.70journal_volume
110pub_type
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