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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
KTH, School of Biotechnology (BIO), Protein Technology. (Chemical Protein Engineering)ORCID iD: 0000-0001-9430-3720
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2014 (English)In: Molecular Imaging, ISSN 1535-3508, E-ISSN 1536-0121, Vol. 13, no 10Article in journal (Refereed) Published
Abstract [en]

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 Cterminus. 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.

Place, publisher, year, edition, pages
2014. Vol. 13, no 10
National Category
Biochemicals Medical Image Processing
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URN: urn:nbn:se:kth:diva-161051ISI: 000349631400003Scopus ID: 2-s2.0-84918563830OAI: oai:DiVA.org:kth-161051DiVA: diva2:793640
Funder
Swedish Research Council
Note

QC 20150309

Available from: 2015-03-09 Created: 2015-03-06 Last updated: 2017-05-19Bibliographically approved

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