Abstract
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 111In- and 68Ga-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.
Original language | English |
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Pages (from-to) | 187-195 |
Number of pages | 9 |
Journal | Cancer Biotherapy and Radiopharmaceuticals |
Volume | 28 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Apr 2013 |
Externally published | Yes |
Keywords
- Affibody molecules
- ER2
- Megalin
- OK cells
- Renal reabsorption
ASJC Scopus subject areas
- Oncology
- Radiology Nuclear Medicine and imaging
- Pharmacology
- Cancer Research