Tumor targeting using affibody molecules: interplay of affinity, target expression level, and binding site composition

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Vladimir TolmachevAnna Orlova

Abstract

Radionuclide imaging of cancer-associated molecular alterations may contribute to patient stratification for targeting therapy. Scaffold high-affinity proteins, such as Affibody molecules, are a new, promising class of probes for in vivo imaging. The effects of human epidermal growth factor receptor 2 (HER2) affinity and binding site composition of HER2-binding Affibody molecules, and of the HER2 density on the tumor targeting, were studied in vivo. The tumor uptake and tumor-to-organ ratios of Affibody molecules with moderate (dissociation constant [K(D)] = 10(-9) M) or high (K(D) = 10(-10) M) affinity were compared between tumor xenografts with a high (SKOV-3) and low (LS174T) HER2 expression level in BALB/C nu/nu mice. Two Affibody molecules with similar affinity (K(D) = 10(-10) M) but having alternative amino acids in the binding site were compared. In SKOV-3 xenografts, uptake was independent of affinity at 4 h after injection, but high-affinity binders provided 2-fold-higher tumor radioactivity retention at 24 h. In LS174T xenografts, uptake of high-affinity probes was already severalfold higher at 4 h after injection, and the difference was increased at 24 h. The clearance rate and tumor-to-organ ratios were influenced b...Continue Reading

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Citations

Mar 14, 2014·European Journal of Nuclear Medicine and Molecular Imaging·Anna OrlovaJohn Löfblom
Dec 21, 2013·Current Opinion in Chemical Engineering·Lawrence A SternBenjamin J Hackel
Jul 22, 2015·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Liang Zhang, Greg M Thurber
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Dec 13, 2019·International Journal of Radiation Biology·Shima ShahsavariSeyed Jalal Hosseinimehr
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Nov 4, 2017·Contrast Media & Molecular Imaging·Vladimir TolmachevAnna Orlova
Apr 27, 2018·Scientific Reports·Vladimir TolmachevAmelie Eriksson Karlström
Mar 15, 2020·Cancers·Vladimir Tolmachev, Anna Orlova
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Jun 27, 2019·International Journal of Molecular Sciences·Anzhelika VorobyevaVladimir Tolmachev
Feb 23, 2020·International Journal of Molecular Sciences·Sara S RinneAnzhelika Vorobyeva
Jan 20, 2021·Seminars in Cancer Biology·Vladimir TolmachevJens Sörensen
Sep 17, 2019·Life Sciences·Sajjad Ahmadpour, Seyed Jalal Hosseinimehr
May 1, 2021·International Journal of Molecular Sciences·Sara S RinneVladimir Tolmachev
Mar 26, 2014·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Jens SörensenHenrik Lindman
Mar 27, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Anna OrlovaVladimir Tolmachev
Feb 26, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Mattias SandströmMark Lubberink
Jan 11, 2014·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Vladimir TolmachevAnna Orlova
Jun 28, 2014·Molecular Pharmaceutics·Joanna StrandVladimir Tolmachev

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