In vivo and in vitro studies on renal uptake of radiolabeled affibody molecules for imaging of HER2 expression in tumors

Mohamed Altai, Zohreh Varasteh, Karl Andersson, Annemarie Eek, Otto Boerman, Anna Orlova

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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 languageEnglish
Pages (from-to)187-195
Number of pages9
JournalCancer Biotherapy and Radiopharmaceuticals
Volume28
Issue number3
DOIs
Publication statusPublished - 1 Apr 2013
Externally publishedYes

Keywords

  • Affibody molecules
  • ER2
  • Megalin
  • OK cells
  • Renal reabsorption

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

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