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Pharmacokinetics and Biodistribution of a [89Zr]Zr-DFO-MSTP2109A Anti-STEAP1 Antibody in Metastatic Castration-Resistant Prostate Cancer Patients

  • Joseph A. O’Donoghue
    Joseph A. O’Donoghue
    Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
  • Daniel C. Danila
    Daniel C. Danila
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
    Department of Medicine, Joan and Sanford I. Weill College of Medicine of Cornell University, New York, New York 10065, United States
  • Neeta Pandit-Taskar
    Neeta Pandit-Taskar
    Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
    Department of Radiology, Joan and Sanford I. Weill Cornell Medical Center, New York, New York 10065, United States
  • Volkan Beylergil
    Volkan Beylergil
    Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
  • Sarah M. Cheal
    Sarah M. Cheal
    Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
  • Stephen E. Fleming
    Stephen E. Fleming
    Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
  • Josef J. Fox
    Josef J. Fox
    Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
    More by Josef J. Fox
  • Shutian Ruan
    Shutian Ruan
    Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
    More by Shutian Ruan
  • Pat B. Zanzonico
    Pat B. Zanzonico
    Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
  • Govind Ragupathi
    Govind Ragupathi
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
  • Serge K. Lyashchenko
    Serge K. Lyashchenko
    Radiochemistry Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
  • Simon P. Williams
    Simon P. Williams
    Genentech, South San Francisco, California 94080, United States
  • Howard I. Scher
    Howard I. Scher
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
    Department of Medicine, Joan and Sanford I. Weill College of Medicine of Cornell University, New York, New York 10065, United States
  • Bernard M. Fine
    Bernard M. Fine
    Genentech, South San Francisco, California 94080, United States
  • John L. Humm
    John L. Humm
    Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
    More by John L. Humm
  • Steven M. Larson
    Steven M. Larson
    Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
    Department of Radiology, Joan and Sanford I. Weill Cornell Medical Center, New York, New York 10065, United States
    Center for Targeted Radioimmunotherapy and Diagnosis of the Ludwig Center for Cancer Immunotherapy, New York, New York 10065, United States
  • Michael J. Morris
    Michael J. Morris
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
    Department of Medicine, Joan and Sanford I. Weill College of Medicine of Cornell University, New York, New York 10065, United States
  • , and 
  • Jorge A. Carrasquillo*
    Jorge A. Carrasquillo
    Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
    Department of Radiology, Joan and Sanford I. Weill Cornell Medical Center, New York, New York 10065, United States
    Center for Targeted Radioimmunotherapy and Diagnosis of the Ludwig Center for Cancer Immunotherapy, New York, New York 10065, United States
    *E-mail: [email protected]. Phone: 212-639-2459. Fax: 212-717-3263.
Cite this: Mol. Pharmaceutics 2019, 16, 7, 3083–3090
Publication Date (Web):May 22, 2019
https://doi.org/10.1021/acs.molpharmaceut.9b00326
Copyright © 2019 American Chemical Society
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Abstract

Abstract Image

A six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a newly identified target in prostate cancer. The use of radio-labeled STEAP1-targeting antibodies with positron emission tomography (PET) may allow for detection of sites of metastatic prostate cancer and may refine patient selection for antigen-directed therapies. This was a prospective study in seven patients with metastatic castration-resistant prostate cancer who had at least one archival biopsy that was STEAP1-positive by immunohistochemistry. Patients received intravenous injections of ∼185 MBq and 10 mg of [89Zr]Zr-DFO-MSTP2109A, a humanized IgG1 monoclonal antibody directed against STEAP1. PET/CT images, blood samples, and whole-body counts were monitored longitudinally in six patients. Here, we report on safety, biodistribution, pharmacokinetics, dose estimates to normal tissues, and initial tumor targeting for this group of patients. There was no significant acute or subacute toxicity. Favorable biodistribution and enhanced lesion uptake (in both bone and soft tissue) were observed on imaging using a mass of 10 mg of DFO-MSTP2109A. The best lesion discrimination was seen at the latest imaging time, a median of 6 days postadministration. Pharmacokinetics showed a median serum T1/2 β of 198 h, volume of central compartment of 3.54 L (similar to plasma volume), and clearance of 19.7 mL/h. The median biologic T1/2 for whole-body retention was 469 h. The highest mean absorbed doses to normal organs (mGy/MBq) were 1.18, 1.11, 0.78, 0.73, and 0.71 for liver, heart wall, lung, kidney, and spleen, respectively. Excellent targeting of metastatic prostate sites in both bone and soft tissue was observed, with an optimal imaging time of 6 days postadministration. The liver and heart were the normal organs that experienced the highest absorbed doses. The pharmacokinetics were similar to other antibodies without major cross-reactivity with normal tissues. A more detailed analysis of lesion targeting in a larger patient population with correlation to immunohistology and standard imaging modalities has been reported.

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This article is cited by 12 publications.

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  2. Weijun Wei, Zachary T. Rosenkrans, Jianjun Liu, Gang Huang, Quan-Yong Luo, Weibo Cai. ImmunoPET: Concept, Design, and Applications. Chemical Reviews 2020, 120 (8) , 3787-3851. https://doi.org/10.1021/acs.chemrev.9b00738
  3. Duygu Yilmaz, Paul S. Sharp, Martin J. Main, Peter B. Simpson. Advanced molecular imaging for the characterisation of complex medicines. Drug Discovery Today 2022, 27 (6) , 1716-1723. https://doi.org/10.1016/j.drudis.2022.03.001
  4. George Crișan, Nastasia Sanda Moldovean-Cioroianu, Diana-Gabriela Timaru, Gabriel Andrieș, Călin Căinap, Vasile Chiș. Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade. International Journal of Molecular Sciences 2022, 23 (9) , 5023. https://doi.org/10.3390/ijms23095023
  5. Felix Dietlein, Carsten Kobe, Sergio Muñoz Vázquez, Thomas Fischer, Heike Endepols, Melanie Hohberg, Manuel Reifegerst, Bernd Neumaier, Klaus Schomäcker, Alexander E. Drzezga, Markus Dietlein. An 89 Zr-Labeled PSMA Tracer for PET/CT Imaging of Prostate Cancer Patients. Journal of Nuclear Medicine 2022, 63 (4) , 573-583. https://doi.org/10.2967/jnumed.121.262290
  6. Maria Silvia De Feo, Mariano Pontico, Viviana Frantellizzi, Ferdinando Corica, Flaminia De Cristofaro, Giuseppe De Vincentis. 89Zr-PET imaging in humans: a systematic review. Clinical and Translational Imaging 2022, 10 (1) , 23-36. https://doi.org/10.1007/s40336-021-00462-9
  7. Tsung-Yi Lin, Jeong A Park, Alan Long, Hong-Fen Guo, Nai-Kong V Cheung. Novel potent anti-STEAP1 bispecific antibody to redirect T cells for cancer immunotherapy. Journal for ImmunoTherapy of Cancer 2021, 9 (9) , e003114. https://doi.org/10.1136/jitc-2021-003114
  8. Vu‐Long Tran, François Lux, Nicolas Tournier, Benoit Jego, Xavier Maître, Maria Anisorac, Claude Comtat, Sébastien Jan, Katalin Selmeczi, Michael J. Evans, Olivier Tillement, Bertrand Kuhnast, Charles Truillet. Quantitative Tissue Pharmacokinetics and EPR Effect of AGuIX Nanoparticles: A Multimodal Imaging Study in an Orthotopic Glioblastoma Rat Model and Healthy Macaque. Advanced Healthcare Materials 2021, 10 (16) , 2100656. https://doi.org/10.1002/adhm.202100656
  9. Guus A.M.S. van Dongen, Wissam Beaino, Albert D. Windhorst, Gerben J.C. Zwezerijnen, Daniela E. Oprea-Lager, N. Harry Hendrikse, Cornelis van Kuijk, Ronald Boellaard, Marc C. Huisman, Danielle J. Vugts. The Role of 89 Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals. Journal of Nuclear Medicine 2021, 62 (4) , 438-445. https://doi.org/10.2967/jnumed.119.239558
  10. Zhi Jiao, Lei Huang, Jiali Sun, Jie Xie, Tiantian Wang, Xiu Yin, Haozheng Zhang, Jie Chen. Six-transmembrane epithelial antigen of the prostate 1 expression promotes ovarian cancer metastasis by aiding progression of epithelial-to-mesenchymal transition. Histochemistry and Cell Biology 2020, 154 (2) , 215-230. https://doi.org/10.1007/s00418-020-01877-7
  11. Wout Oosterheert, Piet Gros. Cryo-electron microscopy structure and potential enzymatic function of human six-transmembrane epithelial antigen of the prostate 1 (STEAP1). Journal of Biological Chemistry 2020, 295 (28) , 9502-9512. https://doi.org/10.1074/jbc.RA120.013690
  12. F. Cortezon-Tamarit, A. Baryzewska, M. Lledos, S.I. Pascu. Zirconium-89 radio-nanochemistry and its applications towards the bioimaging of prostate cancer. Inorganica Chimica Acta 2019, 496 , 119041. https://doi.org/10.1016/j.ica.2019.119041

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