In vivo and in vitro studies on renal uptake of radiolabeled affibody molecules for imaging of HER2 expression in tumors
until further notice
SourceCancer Biotherapy & Radiopharmaceuticals, 28, 3, (2013), pp. 187-195
Altai, Mohamed Varasteh, Zohreh Andersson, Karl Eek, Annemarie Boerman, Otto Orlova, Anna Research Support, Non-U.S. Gov't United States Cancer Biother Radiopharm. 2013 Apr;28(3):187-95. doi: 10.1089/cbr.2012.1304. Epub 2013 Mar 5.
Article / Letter to editor
Display more detailsDisplay less details
Cancer Biotherapy & Radiopharmaceuticals
SubjectNCMLS 6: Genetics and epigenetic pathways of disease; ONCOL 3: Translational research NCMLS 2: Immune Regulation
Affibody molecules (6-7 kDa) are a new class of small robust three-helical scaffold proteins. Radiolabeled subnanomolar anti-HER2 affibody ZHER2:342 was developed for imaging of HER2 expression in tumors, and a clinical study has demonstrated that the (111)In- and (68)Ga-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: KD1=0.8 nM, Bmax1=71,500 and KD2=9.2 nM, Bmax2=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.
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.