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In Vivo and In Vitr...
In Vivo and In Vitro Studies on Renal Uptake of Radiolabeled Affibody Molecules for Imaging of HER2 Expression in Tumors
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- Altai, Mohamed (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Varasteh, Zohreh (författare)
- Uppsala universitet,Plattformen för preklinisk PET
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- Andersson, Karl (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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Eek, Annemarie (författare)
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Boerman, Otto (författare)
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- Orlova, Anna (författare)
- Uppsala universitet,Enheten för nuklearmedicin och PET
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(creator_code:org_t)
- Mary Ann Liebert Inc, 2013
- 2013
- Engelska.
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 28:3, s. 187-195
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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http://uu.diva-porta...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Affibody molecules (6-7 kDa) are a new class of small robust three-helical scaffold proteins. Radiolabeled subnanomolar anti-HER2 affibody Z(HER2:342) was developed for imaging of HER2 expression in tumors, and a clinical study has demonstrated that the In-111- and Ga-68-labeled affibody molecules can efficiently detect HER2 expressing metastases in breast cancer patients. However, a significant renal accumulation of radioactivity after systemic injection of a radiolabeled anti-HER2 affibody conjugate is observed. The aim of this study was to investigate the mechanism of renal reabsorption of anti-HER2 affibody at the molecular level. Renal accumulation of radiolabeled anti-HER2 affibody molecules was studied in a murine model and in vitro using opossum-derived proximal tubule (OK) cells. It was found that kidney reabsorption of affibody molecule was not driven by megalin/cubilin. Amino acids in the target-binding side of affibody molecule were involved in binding to OK cells. On OK cells, two types of receptors for anti-HER2 affibody molecule were found: K-D1 = 0.8 nM, B-max1 = 71,500 and K-D2 = 9.2 nM, B-max2 = 367,000. The results of the present study indicate that affibody molecule and other scaffold-based targeting proteins with a relatively low kidney uptake can be selected using in vitro studies with tubular kidney cells.
Nyckelord
- affibody molecules
- HER2
- OK cells
- megalin
- renal reabsorption
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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