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Comparative Evaluation of Affibody Molecules for Radionuclide Imaging of in Vivo Expression of Carbonic Anhydrase IX
KTH, School of Biotechnology (BIO), Protein Technology.
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2016 (English)In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 13, no 11, p. 3676-3687Article in journal (Refereed) Published
Abstract [en]

Overexpression of the enzyme carbonic anhydrase IX (CAIX) is documented for chronically hypoxic malignant tumors as well as for normoxic renal cell carcinoma. Radionuclide molecular imaging of CAIX would be useful for detection of hypoxic areas in malignant tumors, for patients' stratification for CAIX-targeted therapies, and for discrimination of primary malignant and benign renal tumors. Earlier, we have reported feasibility of in vivo radionuclide based imaging of CAIX expressing tumors using Affibody molecules, small affinity proteins based on a non-immunoglobulin scaffold. In this study, we compared imaging properties of several anti-CAIX Affibody molecules having identical scaffold parts and competing for the same epitope on CAIX, but having different binding paratopes. Four variants were labeled using residualizing Tc-99m and nonresidualizing I-125 labels. All radiolabeled variants demonstrated high affinity detection of CAIX-expressing cell line SK-RC-52 in vitro and specific accumulation in SK-RC-52 xenografts in vivo. I-125-labeled conjugates demonstrated much lower radioactivity uptake in kidneys but higher radioactivity concentration in blood compared with Tc-99m-labeled counterparts. Although all variants cleared rapidly from blood and nonspecific compartments, there was noticeable difference in their biodistribution. The best variant for imaging of expression of CAIX in disseminated cancer was Tc-99m-(HE)(3)-ZCAIX:2 providing tumor uptake of 16.3 +/- 0.9% ID/g and tumor-to-blood ratio of 44 +/- 7 at 4 h after injection. For primary renal cell carcinoma, the most promising imaging candidate was I-125-ZCAIX:4 providing tumor-kidney ratio of 2.1 0.5. In conclusion, several clones of scaffold proteins should be evaluated to select the best variant for development of an imaging probe with optimal sensitivity for the intended application.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2016. Vol. 13, no 11, p. 3676-3687
Keywords [en]
CAIX, affibody molecule, imaging, radionuclide
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:kth:diva-198971DOI: 10.1021/acs.molpharmaceut.6b00502ISI: 000387428300008Scopus ID: 2-s2.0-84994536143OAI: oai:DiVA.org:kth-198971DiVA, id: diva2:1065632
Funder
Swedish Cancer Society, 2014/474Swedish Cancer Society, 2015/350Swedish Research Council, 2015-02353Swedish Research Council, 2015-02509
Note

QC 20170116

Available from: 2017-01-16 Created: 2016-12-22 Last updated: 2017-11-29Bibliographically approved

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Andersson, Ken G.Löfblom, John

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