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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 4/2019

01-08-2019 | Research Article

Preclinical SPECT Imaging of Choroidal Neovascularization in Mice Using Integrin-Binding [99mTc]IDA-D-[c(RGDfK)]2

Authors: Seong Joon Ahn, Ho-Young Lee, Hye Kyoung Hong, Jae Ho Jung, Ji Hyun Park, Kyu Hyung Park, Sang Eun Kim, Se Joon Woo, Byung Chul Lee

Published in: Molecular Imaging and Biology | Issue 4/2019

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Abstract

Purpose

Integrin ɑvβ3, an adhesion molecule overexpressed in neovascular endothelial cells, is involved in ocular angiogenesis. Integrin ɑvβ3-binding arginine–glycine–aspartic acid (RGD) peptide has been used to target and visualize new vessels. We explored the use of integrin ɑvβ3-targeted RGD peptide ([99mTc]IDA-D-[c(RGDfK)]2) 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 [99mTc]IDA-D-[c(RGDfK)]2 and single-photon emission computed tomography (SPECT) images of [99mTc]IDA-D-[c(RGDfK)]2 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)]2 immunofluorescence, in contrast to the normal retina and choroid. Retinal integrin mRNA expression peaked at day 1 following CNV induction. On SPECT images using [99mTc]IDA-D-[c(RGDfK)]2, 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 [99mTc]IDA-D-[c(RGDfK)]2 can detect CNV and its associated angiogenesis in an animal model of CNV.

Conclusions

SPECT imaging using an integrin ɑvβ3-targeted RGD peptide radiotracer may be a useful tool for in vivo functional molecular imaging of CNV.
Appendix
Available only for authorised users
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Metadata
Title
Preclinical SPECT Imaging of Choroidal Neovascularization in Mice Using Integrin-Binding [99mTc]IDA-D-[c(RGDfK)]2
Authors
Seong Joon Ahn
Ho-Young Lee
Hye Kyoung Hong
Jae Ho Jung
Ji Hyun Park
Kyu Hyung Park
Sang Eun Kim
Se Joon Woo
Byung Chul Lee
Publication date
01-08-2019
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 4/2019
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-018-1294-8

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