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Pretargeted ImmunoPET of Prostate Cancer with an Anti-TROP-2 x Anti-HSG Bispecific Antibody in Mice with PC3 Xenografts

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Abstract

Purpose

Pretargeting with bispecific antibodies and radiolabeled hapten-peptides could be used to specifically target tumors with high target-to-background ratios. TF12 is a trivalent bispecific antibody that consists of two anti-TROP-2 Fab fragments and one anti-HSG (histamine-succinyl-glycine) Fab fragment. The TROP-2 antigen is expressed in many epithelial cancers, including prostate cancer (PC), and therefore, this bispecific antibody can be used for pretargeting of PC. In this study, the potential for pretargeted radioimmunoPET with TF12 and the 68Ga-labeled di-HSG peptide IMP288 in mice with human PC xenografts was investigated using 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) as a reference.

Procedures

The potential of pretargeted immunoPET with TF12 and the 68Ga-labeled di-HSG hapten-peptide, IMP288, was studied in mice with subcutaneous PC3 tumors using [18F]FDG as a reference. Furthermore, the use of this pretargeting system for imaging PC lesions was evaluated in mice with intraperitoneally growing tumors with [18F]FDG as a reference.

Results

[68Ga]lMP288 showed rapid accumulation in the TF12 pretargeted subcutaneous tumor (7.2 ± 1.1 % ID/g) with low uptake in the kidneys (1.8 ± 0.5 % ID/g) and high tumor-to-blood ratios (17.4 ± 11.2) at 1 h p.i. Accumulation of [18F]FDG in the s.c. tumors was significantly lower (3.4 ± 0.9 % ID/g, P = 0.008), with lower tumor-to-blood ratios (3.0 ± 1.9, P = 0.011). ImmunoPET/CT images clearly visualized both subcutaneous and intraperitoneal tumors as small as 5 mm3 with low blood levels and kidney uptake as early as 1 h p.i.

Conclusion

Pretargeted immunoPET with TF12 in combination with a 68Ga-labeled hapten-peptide is an efficient system for rapid, sensitive, and specific imaging of prostate cancer.

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References

  1. Beheshti M, Langsteger W, Fogelman I (2009) Prostate cancer: role of SPECT and PET in imaging bone metastases. Semin Nucl Med 39:396–407

    Article  PubMed  Google Scholar 

  2. Ravizzini G, Turkbey B, Kurdziel K et al (2009) New horizons in prostate cancer imaging. Eur J Radiol 70:212–226

    Article  PubMed Central  PubMed  Google Scholar 

  3. Outwater EK, Montilla-Soler JL (2013) Imaging of prostate carcinoma. Cancer Control 20:161–176

    PubMed  Google Scholar 

  4. Lutje S, Boerman OC, van Rij CM et al (2012) Prospects in radionuclide imaging of prostate cancer. Prostate 72:1262–1272

    Article  PubMed  Google Scholar 

  5. Jadvar H (2013) Molecular imaging of prostate cancer with PET. J Nucl Med 54:1685–1688

    Article  CAS  PubMed  Google Scholar 

  6. Hillier SM, Maresca KP, Lu G et al (2013) 99mTc-labeled small-molecule inhibitors of prostate specific membrane antigen for molecular imaging of prostate cancer. J Nucl Med 54:1369–1376

    Article  CAS  PubMed  Google Scholar 

  7. Afshar-Oromieh A, Malcher A, Eder M et al (2013) PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging 40:486–495

    Article  CAS  PubMed  Google Scholar 

  8. van Rij CM, Lutje S, Frielink C et al (2013) Pretargeted immuno-PET and radioimmunotherapy of prostate cancer with an anti-TROP-2 x anti-HSG bispecific antibody. Eur J Nucl Med Mol Imaging 40:1377–1383

    Article  PubMed  Google Scholar 

  9. Basu A, Goldenberg DM, Stein R (1995) The epithelial/carcinoma antigen EGP-1, recognized by monoclonal antibody RS7-3G11, is phosphorylated on serine 303. Int J Cancer 62:472–479

    Article  CAS  PubMed  Google Scholar 

  10. Stein R, Basu A, Chen S et al (1993) Specificity and properties of MAb RS7-3G11 and the antigen defined by this pancarcinoma monoclonal antibody. Int J Cancer 55:938–946

    Article  CAS  PubMed  Google Scholar 

  11. Rossi EA, Goldenberg DM, Cardillo TM et al (2006) Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting. Proc Natl Acad Sci U S A 103:6841–6846

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. McBride WJ, Zanzonico P, Sharkey RM et al (2006) Bispecific antibody pretargeting PET (ImmunoPET) with an 124I-labeled hapten-peptide. J Nucl Med 47:1678–1688

    CAS  PubMed  Google Scholar 

  13. Schoffelen R, Sharkey RM, Goldenberg DM et al (2010) Pretargeted immuno-positron emission tomography imaging of carcinoembryonic antigen-expressing tumors with a bispecific antibody and a 68Ga- and 18F-labeled hapten peptide in mice with human tumor xenografts. Mol Cancer Ther 9:1019–1027

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Brom M, Joosten L, Oyen WJ, Gotthardt M et al (2012) Improved labelling of DTPA- and DOTA-conjugated peptides and antibodies with 111In in HEPES and MES buffer. EJNMMI Res 2:4

    Article  PubMed Central  PubMed  Google Scholar 

  15. Kitajima K, Murphy RC, Nathan MA (2013) Choline PET/CT for imaging prostate cancer: an update. Ann Nucl Med 27:581–591

    Article  CAS  PubMed  Google Scholar 

  16. Ristau BT, O’Keefe DS, Bacich DJ (2014) The prostate-specific membrane antigen: lessons and current clinical implications from 20 years of research. Urol Oncol 323:272–279

    Article  Google Scholar 

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Acknowledgments

We kindly thank Bianca Lemmers, Kitty Lemmens, Iris Lamers-Elemans, and Henk Arnts (Central Animal Facility, Radboud University Medical Center, The Netherlands) for their excellent technical assistance in the animal experiments. The reagents were generously provided by Drs. Chien-Hsing Chang and Edmund Rossi of IBC Pharmaceuticals, Inc. The work was supported by the Dutch Cancer Society (KWF Kankerbestrijding, Grant KUN-2010-0480).

Conflict of Interest

David M. Goldenberg, William J. McBride, and Robert M. Sharkey have financial interests as employment and/or stock interest in Immunomedics, Inc.

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Authors and Affiliations

  1. Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

    Catharina M. van Rij, Cathelijne Frielink, Gerben M. Franssen, Susanne Lütje, Wim J. G. Oyen & Otto C. Boerman

  2. Department of Clinical Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands

    Catharina M. van Rij

  3. Immunomedics, Inc., Morris Plains, NJ, USA

    David M. Goldenberg, Robert M. Sharkey & William J. McBride

  4. Center for Molecular Immunology and the Garden State Cancer Center, Morris Plains, NJ, USA

    David M. Goldenberg

Authors
  1. Catharina M. van Rij
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  2. David M. Goldenberg
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  3. Robert M. Sharkey
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  4. Gerben M. Franssen
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  5. Susanne Lütje
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  6. William J. McBride
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  7. Wim J. G. Oyen
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  8. Otto C. Boerman
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Correspondence to Catharina M. van Rij.

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van Rij, C.M., Frielink, C., Goldenberg, D.M. et al. Pretargeted ImmunoPET of Prostate Cancer with an Anti-TROP-2 x Anti-HSG Bispecific Antibody in Mice with PC3 Xenografts. Mol Imaging Biol 17, 94–101 (2015). https://doi.org/10.1007/s11307-014-0772-x

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  • DOI: https://doi.org/10.1007/s11307-014-0772-x

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