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89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer

  • Neeta Pandit-TaskarEmail author
  • Joseph A. O’Donoghue
  • Volkan Beylergil
  • Serge Lyashchenko
  • Shutian Ruan
  • Stephen B. Solomon
  • Jeremy C. Durack
  • Jorge A. Carrasquillo
  • Robert A. Lefkowitz
  • Mithat Gonen
  • Jason S. Lewis
  • Jason P. Holland
  • Sarah M. Cheal
  • Victor E. Reuter
  • Joseph R. Osborne
  • Massimo F. Loda
  • Peter M. Smith-Jones
  • Wolfgang A. Weber
  • Neil H. Bander
  • Howard I. Scher
  • Michael J. Morris
  • Steven M. Larson
Original Article

Abstract

Purpose

Given the bone tropism of prostate cancer, conventional imaging modalities poorly identify or quantify metastatic disease. 89Zr-huJ591 positron emission tomography (PET) imaging was performed in patients with metastatic prostate cancer to analyze and validate this as an imaging biomarker for metastatic disease. The purpose of this initial study was to assess safety, biodistribution, normal organ dosimetry, and optimal imaging time post-injection for lesion detection.

Methods

Ten patients with metastatic prostate cancer received 5 mCi of 89Zr-huJ591. Four whole-body scans with multiple whole-body count rate measurements and serum activity concentration measurements were obtained in all patients. Biodistribution, clearance, and lesion uptake by 89Zr-huJ591 immuno-PET imaging was analyzed and dosimetry was estimated using MIRD techniques. Initial assessment of lesion targeting of 89Zr-huJ591 was done. Optimal time for imaging post-injection was determined.

Results

The dose was well tolerated with mild chills and rigors seen in two patients. The clearance of 89Zr-huJ591 from serum was bi-exponential with biological half-lives of 7 ± 4.5 h (range 1.1–14 h) and 62 ± 13 h (range 51–89 h) for initial rapid and later slow phase. Whole-body biological clearance was 219 ± 48 h (range 153–317 h). The mean whole-body and liver residence time was 78.7 and 25.6 h, respectively. Dosimetric estimates to critical organs included liver 7.7 ± 1.5 cGy/mCi, renal cortex 3.5 ± 0.4 cGy/mCi, and bone marrow 1.2 ± 0.2 cGy/mCi. Optimal time for patient imaging after injection was 7 ± 1 days. Lesion targeting of bone or soft tissue was seen in all patients. Biopsies were performed in 8 patients for a total 12 lesions, all of which were histologically confirmed as metastatic prostate cancer. One biopsy-proven lesion was not positive on 89Zr-huJ591, while the remaining 11 lesions were 89Zr-huJ591 positive. Two biopsy-positive nodal lesions were noted only on 89Zr-huJ591 study, while the conventional imaging modality was negative.

Conclusion

89Zr-huJ591 PET imaging of prostate-specific membrane antigen expression is safe and shows good localization of disease in prostate cancer patients. Liver is the critical organ for dosimetry, and 7 ± 1 days is the optimal imaging time. A larger study is underway to determine lesion detection in an expanded cohort of patients with metastatic prostate cancer.

Keywords

89Zr-huJ591 J591 antibody Prostate cancer Radioimmunotherapy Dosimetry 

Notes

Acknowledgments

Starr Cancer Consortium, Prostate cancer program of MSKCC and Center for Targeted Radioimmunotherapy and Diagnosis of the Ludwig Center for Cancer Immunotherapy, David H. Koch Foundation, R21 CA153177-03. RMPIC core is supported in part by NIH P30CA008748, the Landy Research Fund, and Hascoe Charitable Foundation.

Conflicts of interest

None.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Neeta Pandit-Taskar
    • 1
    • 9
    Email author
  • Joseph A. O’Donoghue
    • 2
  • Volkan Beylergil
    • 1
  • Serge Lyashchenko
    • 7
  • Shutian Ruan
    • 1
  • Stephen B. Solomon
    • 1
    • 9
  • Jeremy C. Durack
    • 1
    • 9
  • Jorge A. Carrasquillo
    • 1
    • 9
  • Robert A. Lefkowitz
    • 1
    • 9
  • Mithat Gonen
    • 3
  • Jason S. Lewis
    • 1
    • 7
    • 8
    • 9
  • Jason P. Holland
    • 1
    • 15
  • Sarah M. Cheal
    • 1
  • Victor E. Reuter
    • 4
    • 10
  • Joseph R. Osborne
    • 1
    • 9
  • Massimo F. Loda
    • 13
    • 14
  • Peter M. Smith-Jones
    • 1
    • 16
  • Wolfgang A. Weber
    • 1
    • 8
    • 9
  • Neil H. Bander
    • 5
    • 11
  • Howard I. Scher
    • 6
    • 12
  • Michael J. Morris
    • 6
    • 12
  • Steven M. Larson
    • 1
    • 8
    • 9
  1. 1.Department of RadiologyMemorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Department of Medical PhysicsMemorial Sloan Kettering Cancer CenterNew YorkUSA
  3. 3.Department of Epidemiology & BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkUSA
  4. 4.Department of PathologyMemorial Sloan Kettering Cancer CenterNew YorkUSA
  5. 5.Department of SurgeryMemorial Sloan Kettering Cancer CenterNew YorkUSA
  6. 6.Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkUSA
  7. 7.Department of Radiochemistry & Molecular Imaging Probes CoreMemorial Sloan Kettering Cancer CenterNew YorkUSA
  8. 8.Program in Molecular Pharmacology and ChemistryMemorial Sloan Kettering Cancer CenterNew YorkUSA
  9. 9.Department of RadiologyWeill Cornell Medical CollegeNew YorkUSA
  10. 10.Department of PathologyWeill Cornell Medical CollegeNew YorkUSA
  11. 11.Department of UrologyWeill Cornell Medical CollegeNew YorkUSA
  12. 12.Department of MedicineWeill Cornell Medical CollegeNew YorkUSA
  13. 13.Dana-Farber Cancer InstituteBostonUSA
  14. 14.Broad Institute of Harvard and MITCambridgeUSA
  15. 15.Department of Radiology of Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  16. 16.Department of Psychiatry and Behavioral Science of Stony Brook UniversityStony BrookUSA

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