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Article Abstract
Purpose: Integrin ɑβ, an adhesion molecule overexpressed in neovascular endothelial cells, is involved in ocular angiogenesis. Integrin ɑβ-binding arginine-glycine-aspartic acid (RGD) peptide has been used to target and visualize new vessels. We explored the use of integrin ɑβ-targeted RGD peptide ([Tc]IDA-D-[c(RGDfK)]) for in vivo molecular imaging of choroidal neovascularization (CNV).
Procedures: To induce CNV in animals, the right eyes of C57BL/6 mice were treated with retinal argon laser photocoagulation. CNV formation was confirmed on immunohistopathological examination of retinal and choroidal tissues. To explore the association of integrin with angiogenesis, integrin mRNA expression in the retinal and choroidal tissues was measured using real-time reverse transcriptase-polymerase chain reaction. For in vivo imaging, mice were intravenously injected with [Tc]IDA-D-[c(RGDfK)] and single-photon emission computed tomography (SPECT) images of [Tc]IDA-D-[c(RGDfK)] were obtained before laser induction (baseline) and at 1, 3, 7, and 14 days post-induction. CNV-induced regional alterations were measured using radiotracer uptake count.
Results: Immunohistopathological examination revealed that CNV lesions showed intense fluorescein isothiocyanate (FITC)-D-[c(RGDfK)] immunofluorescence, in contrast to the normal retina and choroid. Retinal integrin mRNA expression peaked at day 1 following CNV induction. On SPECT images using [Tc]IDA-D-[c(RGDfK)], the radio-uptake count in eyes with CNV was significantly higher than in normal controls on days 1-7 (all p < 0.05), with a peak at day 3 representing the highest angiogenic activity. Our preclinical data demonstrated that [Tc]IDA-D-[c(RGDfK)] can detect CNV and its associated angiogenesis in an animal model of CNV.
Conclusions: SPECT imaging using an integrin ɑβ-targeted RGD peptide radiotracer may be a useful tool for in vivo functional molecular imaging of CNV.
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