Tumor imaging using a picomolar affinity HER2 binding Affibody molecule

Anna Orlova, Mikaela Magnusson, Tove L.J. Eriksson, Martin Nilsson, Barbro Larsson, Ingmarie Höiden-Guthenberg, Charles Widström, Jörgen Carlsson, Vladimir Tolmachev, Stefan Ståhl, Fredrik Y. Nilsson

Результат исследований: Материалы для журналаСтатьярецензирование

378 Цитирования (Scopus)

Аннотация

The detection of cell-bound proteins that are produced due to aberrant gene expression in malignant tumors can provide important diagnostic information influencing patient management. The use of small radiolabeled targeting proteins would enable high-contrast radionuclide imaging of cancers expressing such antigens if adequate binding affinity and specificity could be provided. Here, we describe a HER2-specific 6 kDa Affibody molecule (hereinafter denoted Affibody molecule) with 22 pmol/L affinity that can be used for the visualization of HER2 expression in tumors in vivo using gamma camera. A library for affinity maturation was constructed by re-randomization of relevant positions identified after the alignment of first-generation variants of nanomolar affinity (50 nmol/L). One selected Affibody molecule, Z HER2:342 showed a >2,200-fold increase in affinity achieved through a single-library affinity maturation step. When radioiodinated, the affinity-matured Affibody molecule showed clear, high-contrast visualization of HER2-expressing xenografts in mice as early as 6 hours post-injection. The tumor uptake at 4 hours post-injection was improved 4-fold (due to increased affinity) with 9% of the injected dose per gram of tissue in the tumor. Affibody molecules represent a new class of affinity molecules that can provide small sized, high affinity cancer-specific ligands, which may be well suited for tumor imaging.

Язык оригиналаАнглийский
Страницы (с-по)4339-4348
Число страниц10
ЖурналCancer Research
Том66
Номер выпуска8
DOI
СостояниеОпубликовано - 15 апр 2006
Опубликовано для внешнего пользованияДа

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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