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Influence of Severa...
Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody Molecules
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- Garousi, Javad (author)
- Uppsala universitet,Uppsala University,Medicinsk strålningsvetenskap
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- Vorobyeva, Anzhelika (author)
- Uppsala universitet,Uppsala University,Tomsk Polytechnic University,Medicinsk strålningsvetenskap,Natl Res Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.
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- Altai, Mohamed (author)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Systemisk strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Systemic radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Kamprad Lab, S-22243 Lund, Sweden.
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(creator_code:org_t)
- 2020-06-09
- 2020
- English.
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In: Molecules (Basel, Switzerland). - : MDPI AG. - 1420-3049 .- 1431-5157. ; 25:11
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- 99mTc
- affibody molecules
- kidney
- radiolabel
- reabsorption
- renal uptake
- affibody molecules
Publication and Content Type
- art (subject category)
- ref (subject category)
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