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

Seong Joon Ahn, Ho Young Lee, Hye Kyoung Hong, Jae Ho Jung, Ji Hyun Park, Kyuhyung Park, Sang Eun Kim, Se Joon Woo, Byung Chul Lee

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)644-653
Number of pages10
JournalMolecular Imaging and Biology
Volume21
Issue number4
DOIs
StatePublished - 15 Aug 2019

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Choroidal Neovascularization
Single-Photon Emission-Computed Tomography
Integrins
Molecular Imaging
Lasers
Animal Rights
99mTc-IDA-D-(c(RGDfK))2
Dilatation and Curettage
Messenger RNA
Choroid
Light Coagulation
Argon
Reverse Transcriptase Polymerase Chain Reaction
Fluorescein
Radio
Inbred C57BL Mouse
Fluorescent Antibody Technique
Retina
Real-Time Polymerase Chain Reaction
Endothelial Cells

Keywords

  • Age-related macular degeneration
  • Choroidal neovascularization
  • Functional imaging
  • Integrin
  • Molecular imaging
  • RGD peptide

Cite this

@article{06c809b4cb61463abeed9a860e33f3e0,
title = "Preclinical SPECT Imaging of Choroidal Neovascularization in Mice Using Integrin-Binding [99mTc]IDA-D-[c(RGDfK)]2",
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.",
keywords = "Age-related macular degeneration, Choroidal neovascularization, Functional imaging, Integrin, Molecular imaging, RGD peptide",
author = "Ahn, {Seong Joon} and Lee, {Ho Young} and Hong, {Hye Kyoung} and Jung, {Jae Ho} and Park, {Ji Hyun} and Kyuhyung Park and Kim, {Sang Eun} and Woo, {Se Joon} and Lee, {Byung Chul}",
year = "2019",
month = "8",
day = "15",
doi = "10.1007/s11307-018-1294-8",
language = "English",
volume = "21",
pages = "644--653",
journal = "Molecular Imaging and Biology",
issn = "1536-1632",
publisher = "Springer New York",
number = "4",

}

Preclinical SPECT Imaging of Choroidal Neovascularization in Mice Using Integrin-Binding [99mTc]IDA-D-[c(RGDfK)]2 . / Ahn, Seong Joon; Lee, Ho Young; Hong, Hye Kyoung; Jung, Jae Ho; Park, Ji Hyun; Park, Kyuhyung; Kim, Sang Eun; Woo, Se Joon; Lee, Byung Chul.

In: Molecular Imaging and Biology, Vol. 21, No. 4, 15.08.2019, p. 644-653.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Preclinical SPECT Imaging of Choroidal Neovascularization in Mice Using Integrin-Binding [99mTc]IDA-D-[c(RGDfK)]2

AU - Ahn, Seong Joon

AU - Lee, Ho Young

AU - Hong, Hye Kyoung

AU - Jung, Jae Ho

AU - Park, Ji Hyun

AU - Park, Kyuhyung

AU - Kim, Sang Eun

AU - Woo, Se Joon

AU - Lee, Byung Chul

PY - 2019/8/15

Y1 - 2019/8/15

N2 - 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.

AB - 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.

KW - Age-related macular degeneration

KW - Choroidal neovascularization

KW - Functional imaging

KW - Integrin

KW - Molecular imaging

KW - RGD peptide

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U2 - 10.1007/s11307-018-1294-8

DO - 10.1007/s11307-018-1294-8

M3 - Article

VL - 21

SP - 644

EP - 653

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

SN - 1536-1632

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ER -