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Comparative evaluation of affibody- and antibody fragments-based CAIX imaging probes in mice bearing renal cell carcinoma xenografts
Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..ORCID iD: 0000-0002-7224-6304
Radboud Univ Nijmegen, Dept Radiat Oncol, Med Ctr, Nijmegen, Netherlands..
Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..ORCID iD: 0000-0002-4778-3909
Uppsala Univ, Dept Med Chem, Uppsala, Sweden..
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 14907Article in journal (Refereed) Published
Abstract [en]

Carbonic anhydrase IX (CAIX) is a cancer-associated molecular target for several classes of therapeutics. CAIX is overexpressed in a large fraction of renal cell carcinomas (RCC). Radionuclide molecular imaging of CAIX-expression might offer a non-invasive methodology for stratification of patients with disseminated RCC for CAIX-targeting therapeutics. Radiolabeled monoclonal antibodies and their fragments are actively investigated for imaging of CAIX expression. Promising alternatives are small non-immunoglobulin scaffold proteins, such as affibody molecules. A CAIX-targeting affibody ZCAIX:2 was re-designed with the aim to decrease off-target interactions and increase imaging contrast. The new tracer, DOTA-HE3-ZCAIX:2, was labeled with In-111 and characterized in vitro. Tumor-targeting properties of [In-111]In-DOTA-HE3-ZCAIX:2 were compared head-to-head with properties of the parental variant, [(99)mTc]Tc(CO)(3)-HE3-ZCAIX:2, and the most promising antibody fragment-based tracer, [In-111]In-DTPA-G250(Fab')(2), in the same batch of nude mice bearing CAIX-expressing RCC xenografts. Compared to the (99)mTc-labeled parental variant, [In-111]In-DOTA-HE3-ZCAIX:2 provides significantly higher tumor-to-lung, tumor-to-bone and tumor-to-liver ratios, which is essential for imaging of CAIX expression in the major metastatic sites of RCC. [In-111]In-DOTA-HE3-ZCAIX:2 offers significantly higher tumor-to-organ ratios compared with [In-111]In-G250(Fab']2. In conclusion, [In-111]In-DOTA-HE3-ZCAIX:2 can be considered as a highly promising tracer for imaging of CAIX expression in RCC metastases based on our results and literature data.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 9, article id 14907
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Radiology, Nuclear Medicine and Medical Imaging
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URN: urn:nbn:se:kth:diva-263340DOI: 10.1038/s41598-019-51445-wISI: 000490702200022PubMedID: 31624303Scopus ID: 2-s2.0-85073512499OAI: oai:DiVA.org:kth-263340DiVA, id: diva2:1375968
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QC 20191206

Available from: 2019-12-06 Created: 2019-12-06 Last updated: 2019-12-06Bibliographically approved

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Andersson, Ken G.Leitao, Charles DahlssonLöfblom, John

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