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Published in: European Journal of Nuclear Medicine and Molecular Imaging 11/2014

01-11-2014 | Original Article

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

Authors: Neeta Pandit-Taskar, 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

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2014

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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.
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Metadata
Title
89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer
Authors
Neeta Pandit-Taskar
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
Publication date
01-11-2014
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2014
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-014-2830-7

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