Position for site-specific attachment of a DOTA chelator to synthetic affibody molecules has a different influence on the targeting properties of 68Ga- compared to 111in-labeled conjugates.

Abstract

Affibody molecules, small (7 kDa) scaffold proteins, are a promising class of probes for radionuclide molecular imaging. Radiolabeling of Affibody molecules with the positron-emitting nuclide 68Ga would permit the use of positron emission tomography (PET), providing better resolution, sensitivity, and quantification accuracy than single-photon emission computed tomography (SPECT). The synthetic anti-HER2 ZHER2:S1 Affibody molecule was conjugated with DOTA at the N-terminus, in the middle of helix 3, or at the C-terminus. The biodistribution of 68Ga- and 111In-labeled Affibody molecules was directly compared in NMRI nu/nu mice bearing SKOV3 xenografts. The position of the chelator strongly influenced the biodistribution of the tracers, and the influence was more pronounced for 68Ga-labeled Affibody molecules than for the 111In-labeled counterparts. The best 68Ga-labeled variant was 68Ga-[DOTA-A1]-ZHER2:S1, which provided a tumor uptake of 13 ± 1 %ID/g and a tumor to blood ratio of 39 ± 12 at 2 hours after injection. 111In-[DOTA-A1]-ZHER2:S1 and 111In-[DOTA-K58]-ZHER2:S1 were equally good at this time point, providing a tumor uptake of 15 to 16 %ID/g and a tumor to blood ratio in the range of 60 to 80. In conclusion, the selection of the best position for a chelator in Affibody molecules can be used for optimization of their imaging properties. This may be important for the development of Affibody-based and other protein-based imaging probes.

• Authors: Hadis Honarvar, Joanna Strand, Anna Perols, Anna Orlova, Ram Kumar Selvaraju, Amelie Eriksson Karlström, Vladimir Tolmachev
• Journal: Molecular imaging (Mol Imaging) Vol. 13 ( 2014) ISSN: 1536-0121 [Electronic] England
• PMID: 25249017 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chelating Agents
• Gallium Radioisotopes
• Heterocyclic Compounds, 1-Ring
• Indium Radioisotopes
• Recombinant Fusion Proteins
• affibody Z(HER2-S1)
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Topics

• Animals
• Cell Line, Tumor
• Chelating Agents (chemistry)
• Female
• Gallium Radioisotopes (pharmacokinetics)
• Heterocyclic Compounds, 1-Ring (chemistry)
• Humans
• Indium Radioisotopes (pharmacokinetics)
• Isotope Labeling
• Mice
• Neoplasm Transplantation
• Ovarian Neoplasms (diagnostic imaging)
• Positron-Emission Tomography
• Recombinant Fusion Proteins (chemical synthesis)