TY - JOUR
T1 - Comparative evaluation of anti-HER2 affibody molecules labeled with 64Cu using NOTA and NODAGA
AU - Tolmachev, Vladimir
AU - Yim, Cheng Bin
AU - Rajander, Johan
AU - Perols, Anna
AU - Karlström, Amelie Eriksson
AU - Haaparanta-Solin, Merja
AU - Grönroos, Tove J.
AU - Solin, Olof
AU - Orlova, Anna
N1 - Funding Information:
This research was financially supported by grants from the Swedish Cancer Society [Grants CAN 2015/350 and 2014/474], Swedish Research Council [Grants 2015-02353, 2013-5135, and 2015-02509], and Hospital District of Southwest Finland (EVO).
Publisher Copyright:
© 2017 Vladimir Tolmachev et al.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2017/2/28
Y1 - 2017/2/28
N2 - Imaging using affibody 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 64Cu (T1/2 = 12. 7h) would make 64Cu a superior nuclide compared to 68Ga 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 64Cu. The tumor-targeting properties of 64Cu-NOTA-ZHER2:S1 and 64Cu-NODAGA-ZHER2:S1 were evaluated and compared with the targeting properties of 68Ga-NODAGA-ZHER2:S1 in mice. Both 64Cu-NOTA-ZHER2:S1 and 64Cu-NODAGA-ZHER2:S1 demonstrated specific targeting of HER2-expressing xenografts. At 2 h after injection of 64Cu-NOTA-ZHER2:S1,64Cu-NODAGA-ZHER2:S1, and 68Ga-NODAGAZHER2: S1, tumor uptakes did not differ significantly. Renal uptake of 64Cu-labeled conjugates was 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 post injection. Organ uptake was lower for 64Cu-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.
AB - Imaging using affibody 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 64Cu (T1/2 = 12. 7h) would make 64Cu a superior nuclide compared to 68Ga 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 64Cu. The tumor-targeting properties of 64Cu-NOTA-ZHER2:S1 and 64Cu-NODAGA-ZHER2:S1 were evaluated and compared with the targeting properties of 68Ga-NODAGA-ZHER2:S1 in mice. Both 64Cu-NOTA-ZHER2:S1 and 64Cu-NODAGA-ZHER2:S1 demonstrated specific targeting of HER2-expressing xenografts. At 2 h after injection of 64Cu-NOTA-ZHER2:S1,64Cu-NODAGA-ZHER2:S1, and 68Ga-NODAGAZHER2: S1, tumor uptakes did not differ significantly. Renal uptake of 64Cu-labeled conjugates was 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 post injection. Organ uptake was lower for 64Cu-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.
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U2 - 10.1155/2017/8565802
DO - 10.1155/2017/8565802
M3 - Article
C2 - 29097939
AN - SCOPUS:85015751435
VL - 2017
JO - Contrast Media and Molecular Imaging
JF - Contrast Media and Molecular Imaging
SN - 1555-4309
M1 - 8565802
ER -