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07.02.2018 | Original Article

Development of an inflammation imaging tracer, 111In-DOTA-DAPTA, targeting chemokine receptor CCR5 and preliminary evaluation in an ApoE−/− atherosclerosis mouse model

Zeitschrift:
Journal of Nuclear Cardiology
Autoren:
PhD Lihui Wei, Julia Petryk, BSc Chantal Gaudet, PhD Maryam Kamkar, PhD Wei Gan, MSc Yin Duan, MD Terrence D. Ruddy
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s12350-018-1203-1) contains supplementary material, which is available to authorized users.
The authors of this article have provided a PowerPoint file, available for download at SpringerLink, which summarises the contents of the paper and is free for re-use at meetings and presentations. Search for the article DOI on SpringerLink.com.

Abstract

Background

Chemokine receptor 5 (CCR5) plays an important role in atherosclerosis. Our objective was to develop a SPECT tracer targeting CCR5 for imaging plaque inflammation by radiolabeling D-Ala-peptide T-amide (DAPTA), a CCR5 antagonist, with 111In.

Methods

1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugated DAPTA (DOTA-DAPTA) was labeled with 111In. Cell uptake studies were conducted in U87-CD4-CCR5 and U87-MG cells. Biodistribution was determined in C57BL/6 mice. Autoradiography, en face and Oil Red O (ORO) imaging studies were performed in ApoE−/− mice.

Results

DOTA-DAPTA was radiolabeled with 111In with high radiochemical purity (> 98%) and specific activity (70 MBq·nmol). 111In-DOTA-DAPTA exhibited fast blood and renal clearance and high spleen uptake. The U87-CD4-CCR5 cells had significantly higher uptake in comparison to the U87-MG cells. The cell uptake was reduced by three times with DAPTA, indicating the receptor specificity of the uptake. Autoradiographic images showed significantly higher lesion uptake of 111In-DOTA-DAPTA in ApoE−/− mice than that in C57BL/6 mice. The tracer uptake in 4 month old ApoE−/− high fat diet (HFD) mice with blocking agent was twofold lower than the same mice without the blocking agent, demonstrating the specificity of the tracer for the CCR5 receptor.

Conclusion

111In-DOTA-DAPTA, specifically targeting chemokine receptor CCR5, is a potential SPECT agent for imaging inflammation in atherosclerosis.

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