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

Authors
  • Garousi, Javad1
  • Vorobyeva, Anzhelika1, 2
  • Altai, Mohamed3
  • 1 (A.V.)
  • 2 Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634 050 Tomsk, Russia
  • 3 Division of Oncology and Pathology, Kamprad Lab, Department of Clinical Sciences, Lund University, 222 43 Lund, Sweden
Type
Published Article
Journal
Molecules
Publisher
MDPI AG
Publication Date
Jun 09, 2020
Volume
25
Issue
11
Identifiers
DOI: 10.3390/molecules25112673
PMID: 32526905
PMCID: PMC7321166
Source
PubMed Central
Keywords
Disciplines
  • Article
License
Green

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 mechanism is the disruption of ATP-mediated cellular uptake and endocytosis processes of affibody molecules by tubular cells.

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