Synthesis and characterization of 64Cu- and Cy5.5-labeled tetraiodothyroacetic acid derivatives for tumor angiogenesis imaging.
Bioorg Med Chem
; 28(1): 115212, 2020 01 01.
Article
in En
| MEDLINE
| ID: mdl-31761727
ABSTRACT
It was previously reported that tetraiodothyroacetic acid (tetrac) inhibits angiogenesis by binding to the cell surface receptor for thyroid hormone on integrin αVß3. Therefore, we synthesized and evaluated two 64Cu-labeled tetrac derivatives and a Cy5.5-labeled tetrac derivative for tumor angiogenesis imaging. Tetrac was structurally modified to conjugate with 1,4,7,10-tetraazacyclododecane-N,N',Nâ³,Nâ³'-tetraacetic acid (DOTA) via its hydroxy or carboxylic acid end, and the resulting DOTA-conjugated tetrac derivatives were then labeled with 64Cu. Tetrac was also conjugated with Cy5.5 via its carboxylic acid end. All three tetrac derivatives (1-3) exhibited greater inhibitory activity than tetrac against endothelial cell tube formation. The U87MG cell binding of [64Cu]2 showed a time-dependent increase over 24â¯h and it was inhibited by 38% at 4â¯h in the presence of tetrac, indicating specificity of [64Cu]2 to the thyroid hormone receptor site on integrin αVß3. Positron emission tomography (PET) images of U87MG tumor-bearing mice injected with [64Cu]1 and [64Cu]2 revealed that high radioactivity accumulated in the tumors, and that the tumor uptake and tumor-to-nontarget uptake ratio were higher in small tumors than in large tumors. In addition, the Cy5.5-labeled tetrac derivative (3) displayed a strong near-infrared (NIR) signal in the tumors. Taken together, these results suggest that these ligands hold promise as imaging agents for visualization of tumor angiogenesis.
Full text:
1
Database:
MEDLINE
Main subject:
Thyroxine
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Brain Neoplasms
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Carbocyanines
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Positron-Emission Tomography
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Neovascularization, Pathologic
Limits:
Animals
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Humans
Language:
En
Year:
2020
Type:
Article