Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody Molecules
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....
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/11/2673 |
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| author | Javad Garousi Anzhelika Vorobyeva Mohamed Altai |
| author_facet | Javad Garousi Anzhelika Vorobyeva Mohamed Altai |
| author_sort | Javad Garousi |
| collection | DOAJ |
| description | 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 [<sup>99m</sup>Tc]Tc-Z<sub>HER:2395</sub> 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 [<sup>99m</sup>Tc]Tc-Z<sub>HER2:2395</sub> 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. |
| first_indexed | 2024-03-10T19:17:24Z |
| format | Article |
| id | doaj.art-e07938cfcd95479d93723e31d98eea03 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T19:17:24Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-e07938cfcd95479d93723e31d98eea032023-11-20T03:17:39ZengMDPI AGMolecules1420-30492020-06-012511267310.3390/molecules25112673Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody MoleculesJavad Garousi0Anzhelika Vorobyeva1Mohamed Altai2Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, SwedenDivision of Oncology and Pathology, Kamprad Lab, Department of Clinical Sciences, Lund University, 222 43 Lund, SwedenAffibody 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 [<sup>99m</sup>Tc]Tc-Z<sub>HER:2395</sub> 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 [<sup>99m</sup>Tc]Tc-Z<sub>HER2:2395</sub> 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.https://www.mdpi.com/1420-3049/25/11/2673affibody moleculesradiolabel<sup>99m</sup>Tckidneyreabsorptionrenal uptake |
| spellingShingle | Javad Garousi Anzhelika Vorobyeva Mohamed Altai Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody Molecules Molecules affibody molecules radiolabel <sup>99m</sup>Tc kidney reabsorption renal uptake |
| title | Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody Molecules |
| title_full | Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody Molecules |
| title_fullStr | Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody Molecules |
| title_full_unstemmed | Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody Molecules |
| title_short | Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody Molecules |
| title_sort | influence of several compounds and drugs on the renal uptake of radiolabeled affibody molecules |
| topic | affibody molecules radiolabel <sup>99m</sup>Tc kidney reabsorption renal uptake |
| url | https://www.mdpi.com/1420-3049/25/11/2673 |
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