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PET imaging of insulin-like growth factor type 1 receptor expression with a 64Cu-labeled Affibody molecule

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Abstract

The insulin-like growth factor 1 receptor (IGF-1R) serves as an attractive target for cancer molecular imaging and therapy. Previous single photon emission computerized tomography (SPECT) studies showed that the IGF-1R-targeting Affibody molecules 99mTc-ZIGF1R:4551-GGGC, [99mTc(CO)3]+-(HE)3-ZIGF1R:4551 and 111In-DOTA-ZIGF1R:4551 can discriminate between high and low IGF-1R-expression tumors and have the potential for patient selection for IGF-1R-targeted therapy. Compared with SPECT, positron emission tomography (PET) may improve imaging of IGF-1R-expression, because of its high sensitivity, high spatial resolution, strong quantification ability. The aim of the present study was to develop the 64Cu-labeled NOTA-conjugated Affibody molecule ZIGF-1R:4:40 as a PET probe for imaging of IGF-1R-positive tumor. An Affibody analogue (Ac-Cys-ZIGF-1R:4:40) binding to IGF-1R was site-specifically conjugated with NOTA and labeled with 64Cu. Binding affinity and specificity of 64Cu-NOTA-ZIGF-1R:4:40 to IGF-1R were evaluated using human glioblastoma U87MG cells. Small-animal PET, biodistribution, and metabolic stability studies were conducted on mice bearing U87MG xenografts after the injection of 64Cu-NOTA-ZIGF-1R:4:40 with or without co-injection of unlabeled Affibody proteins. The radiosynthesis of 64Cu-NOTA-ZIGF-1R:4:40 was completed successfully within 60 min with a decay-corrected yield of 75 %. 64Cu-NOTA-ZIGF-1R:4:40 bound to IGF-1R with low nanomolar affinity (K D = 28.55 ± 3.95 nM) in U87MG cells. 64Cu-NOTA-ZIGF-1R:4:40 also displayed excellent in vitro and in vivo stability. In vivo biodistribution and PET studies demonstrated targeting of U87MG gliomas xenografts was IGF-1R specific. The tumor uptake was 5.08 ± 1.07 %ID/g, and the tumor to muscle ratio was 11.89 ± 2.16 at 24 h after injection. Small animal PET imaging studies revealed that 64Cu-NOTA-ZIGF-1R:4:40 could clearly identify U87MG tumors with good contrast at 1–24 h after injection. This study demonstrates that 64Cu-NOTA-ZIGF-1R:4:40 is a promising PET probe for imaging IGF-1R positive tumor.

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Acknowledgments

This work was supported in part by the Office of Science (BER), US Department of Energy (DE-SC0008397), National Natural Science Foundation of China (81071182) and Medical Innovation Foundation of Fujian, China (2009-CXB-46).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The animal procedures were performed according to a protocol approved by the Stanford University Institutional Animal Care and Use Committee. This article does not contain any studies with human participants performed by any of the authors.

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Not available since no human study was involved.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Zhongshan Hospital Xiamen University, Xiamen, China

    Xinhui Su

  2. Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Bio-X Program and Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Xinhui Su, Kai Cheng, Yang Liu, Xiang Hu, Shuxian Meng & Zhen Cheng

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  1. Xinhui Su
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  2. Kai Cheng
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  3. Yang Liu
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  4. Xiang Hu
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Correspondence to Zhen Cheng.

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Handling Editor: G. Lubec.

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Su, X., Cheng, K., Liu, Y. et al. PET imaging of insulin-like growth factor type 1 receptor expression with a 64Cu-labeled Affibody molecule. Amino Acids 47, 1409–1419 (2015). https://doi.org/10.1007/s00726-015-1975-4

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  • DOI: https://doi.org/10.1007/s00726-015-1975-4

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