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Amino Acids

, Volume 47, Issue 7, pp 1409–1419 | Cite as

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

  • Xinhui Su
  • Kai Cheng
  • Yang Liu
  • Xiang Hu
  • Shuxian Meng
  • Zhen ChengEmail author
Original Article

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.

Keywords

Affibody IGF-1R PET 64Cu NOTA 

Notes

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.

Informed consent

Not available since no human study was involved.

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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Xinhui Su
    • 1
    • 2
  • Kai Cheng
    • 2
  • Yang Liu
    • 2
  • Xiang Hu
    • 2
  • Shuxian Meng
    • 2
  • Zhen Cheng
    • 2
    Email author
  1. 1.Department of Nuclear MedicineZhongshan Hospital Xiamen UniversityXiamenChina
  2. 2.Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Bio-X Program and Stanford Cancer CenterStanford University School of MedicineStanfordUSA

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