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Comparative Evaluation of Anti-HER2 Affibody Molecules Labeled with Cu-64 Using NOTA and NODAGA
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
Univ Turku, Turku PET Ctr, POB 52, Turku 20521, Finland.;Abo Akad Univ, Turku PET Ctr, POB 52, Turku 20521, Finland..
Abo Akad Univ, Turku PET Ctr, POB 52, Turku 20521, Finland..
KTH Royal Inst Technol, Sch Biotechnol, Div Prot Technol, S-10691 Stockholm, Sweden..
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2017 (English)In: Contrast Media & Molecular Imaging, ISSN 1555-4309, E-ISSN 1555-4317, 1-12 p.Article in journal (Refereed) Published
Abstract [en]

Imaging using affi body molecules enables discrimination between breast cancer metastases with high and low expression of HER2, making appropriate therapy selection possible. This study aimed to evaluate if the longer half-life of Cu-64 (T-1/2 = 12.7h) would make Cu-64 a superior nuclide compared to Ga-68 for PET imaging of HER2 expression using affibody molecules. The synthetic ZHER2: S1 affibody molecule was conjugated with the chelators NOTA or NODAGA and labeled with Cu-64. The tumor-targeting properties of Cu-64-NOTA-ZHER2: S1 and Cu-64-NODAGA-ZHER2: S1 were evaluated and compared with the targeting properties of Ga-68-NODAGA-ZHER2: S1 in mice. Both 64 Cu-NOTA-ZHER2: S1 and Cu-64-NODAGA-ZHER2: S1 demonstrated specific targeting of HER2-expressing xenografts. At 2 h after injection of Cu-64-NOTA-ZHER2: S1, Cu-64-NODAGA-ZHER2: S1, and Ga-68-NODAGAZHER2: S1, tumor uptakes did not differ significantly. Renal uptake of Cu-64-labeled conjugateswas dramatically reduced at 6 and 24 h after injection. Notably, radioactivity uptake concomitantly increased in blood, lung, liver, spleen, and intestines, which resulted in decreased tumor-to-organ ratios compared to 2 h postinjection. Organ uptake was lower for Cu-64-NODAGA-ZHER2: S1. The most probable explanation for this biodistribution pattern was the release and redistribution of renal radiometabolites. In conclusion, monoamide derivatives of NOTA and NODAGA may be suboptimal chelators for radiocopper labeling of anti-HER2 affibody molecules and, possibly, other scaffold proteins with high renal uptake.

Place, publisher, year, edition, pages
WILEY-HINDAWI , 2017. 1-12 p.
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-322000DOI: 10.1155/2017/8565802ISI: 000399198500001OAI: oai:DiVA.org:uu-322000DiVA: diva2:1095592
Funder
Swedish Cancer Society, CAN 2015/350 2014/474Swedish Research Council, 2015-02353 2013-5135 2015-02509
Available from: 2017-05-15 Created: 2017-05-15 Last updated: 2017-05-31Bibliographically approved

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