Amino Acids

, Volume 51, Issue 10–12, pp 1569–1575 | Cite as

Preclinical evaluation of a 64Cu-labeled disintegrin for PET imaging of prostate cancer

  • Hossein JadvarEmail author
  • Kai Chen
  • Ryan Park
  • Li-Peng Yap
  • Ivetta Vorobyova
  • Steve Swenson
  • Francis S. Markland
Original Article


A novel recombinant disintegrin, vicrostatin (VCN), displays high binding affinity to a broad range of human integrins in substantial competitive biological advantage over other integrin-based antagonists. In this study, we synthesized a new 64Cu-labeled VCN probe and evaluated its imaging properties for prostate cancer in PC-3 tumor-bearing mice. Macrocyclic chelating agent 1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosine (DiAmSar) was conjugated with PEG unit and followed by coupling with VCN. The precursor was then radiolabeled with positron emitter 64Cu (t1/2 = 12.7 h) in ammonium acetate buffer to provide 64Cu-Sar-PEG-VCN, which was subsequently subjected to in vitro studies, small animal PET, and biodistribution studies. The PC-3 tumor-targeting efficacy of 64Cu-Sar-PEG-VCN was compared to a cyclic RGD peptide-based PET probe (64Cu-Sar-RGD). 64Cu labeling was achieved in 75% decay-corrected yield with radiochemical purity of  > 98%. The specific activity of 64Cu-Sar-PEG-VCN was estimated to be 37 MBq/nmol. MicroPET imaging results showed that 64Cu-Sar-PEG-VCN has preferential tumor uptake and good tumor retention in PC-3 tumor xenografts. As compared to 64Cu-Sar-RGD, 64Cu-Sar-PEG-VCN produces higher tumor-to-muscle (T/M) imaging contrast ratios at 2 h (4.66 ± 0.34 vs. 2.88 ± 0.46) and 24 h (4.98 ± 0.80 vs. 3.22 ± 0.30) post-injection (pi) and similar tumor-to-liver ratios at 2 h (0.43 ± 0.09 vs. 0.37 ± 0.04) and 24 h (0.57 ± 0.13 vs. 0.52 ± 0.07) pi. The biodistribution results were consistent with the quantitative analysis of microPET imaging, demonstrating good T/M ratio (2.73 ± 0.36) of 64Cu-Sar-PEG-VCN at 48 h pi in PC-3 tumor xenografts. For both microPET and biodistribution studies at 48 h pi, the PC-3 tumor uptake of 64Cu-Sar-PEG-VCN is lower than that of 64Cu-Sar-RGD. 64Cu-Sar-PEG-VCN has the potential for in vivo imaging of prostate cancer with PET, which may provide a unique non-invasive method to quantitatively localize and characterize prostate cancer.


PET imaging Disintegrin Vicrostatin Angiogenesis 64Cu Prostate cancer 



This work was supported by the Southern California Clinical and Translational Science Institute (SC CTSI) at the University of Southern California through grant UL1TR001855 from the National Center for Advancing Translational Science, and grants S10OD012371 and P30CA014089 from the National Cancer Institute of the National Institutes of Health.  The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.  The authors acknowledge Karen Wong and Jennifer Choi for their assistance with data acquisition and analysis.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare. FSM and SS are co-founders of Disintegrin Therapeutics, Inc., but have no financial interest or official role in the Company.

Ethical approval

All procedures performed in this study involving animals were in accordance with the ethical standards of the Institutional Animal Care and Use Committee (IACUC) at the University of Southern California (USC). This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

726_2019_2794_MOESM1_ESM.docx (311 kb)
Supplementary material 1 (DOCX 311 kb)


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Molecular Imaging Center, Department of Radiology, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Department of Biochemistry and Molecular Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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