Development of an inflammation imaging tracer, {sup 111}In-DOTA-DAPTA, targeting chemokine receptor CCR5 and preliminary evaluation in an ApoE{sup −/−} atherosclerosis mouse model
- Nordion Inc. (Canada)
- University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine (Canada)
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 {sup 111}In. Methods: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugated DAPTA (DOTA-DAPTA) was labeled with {sup 111}In. 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{sup −/−} mice. Results: DOTA-DAPTA was radiolabeled with {sup 111}In with high radiochemical purity (> 98%) and specific activity (70 MBq·nmol). {sup 111}In-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 {sup 111}In-DOTA-DAPTA in ApoE{sup −/−} mice than that in C57BL/6 mice. The tracer uptake in 4 month old ApoE{sup −/−} 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: {sup 111}In-DOTA-DAPTA, specifically targeting chemokine receptor CCR5, is a potential SPECT agent for imaging inflammation in atherosclerosis.
- OSTI ID:
- 22962007
- Journal Information:
- Journal of Nuclear Cardiology (Online), Vol. 26, Issue 4; Other Information: Copyright (c) 2019 American Society of Nuclear Cardiology; Country of input: International Atomic Energy Agency (IAEA); ISSN 1532-6551
- Country of Publication:
- United States
- Language:
- English
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