Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody Molecules.

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Javad GarousiMohamed Altai

Abstract

Affibody molecules are the most studied class of engineered scaffold proteins (ESPs) in radionuclide molecular imaging. Attempts to use affibody molecules directly labelled with radiometals for targeted radionuclide therapy were hampered by the high uptake and retention of radioactivity in kidneys. Several promising strategies have been implemented to circumvent this problem. Here, we investigated whether a pharmacological approach targeting different components of the reabsorption system could be used to lower the uptake of [99mTc]Tc-ZHER:2395 affibody molecule in kidneys. Pre-injection of probenecid, furosemide, mannitol or colchicine had no influence on activity uptake in kidneys compared to the control group. Mice pre-injected with maleate and fructose had 33% and 51% reduction in the kidney-associated activity, respectively, compared to the control group. Autoradiography images showed that the accumulation of activity after [99mTc]Tc-ZHER2:2395 injection was in the renal cortex and that both maleate and fructose could significantly reduce it. Results from this study demonstrate that pharmacological intervention with maleate and fructose was effective in reducing the kidney uptake of affibody molecules. A presumable mechani...Continue Reading

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Citations

Oct 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anzhelika VorobyevaJavad Garousi
Jul 30, 2021·Current Opinion in Chemical Biology·Dora Mugoli ChigohoSophie Hernot

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