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

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

Authors:	Pandit-Taskar, N.; O'Donoghue, J. A.; Beylergil, V.; Lyashchenko, S.; Ruan, S.; Solomon, S. B.; Durack, J. C.; Carrasquillo, J. A.; Lefkowitz, R. A.; Gonen, M.; Lewis, J. S.; Holland, J. P.; Cheal, S. M.; Reuter, V. E.; Osborne, J. R.; Loda, M. F.; Smith-Jones, P. M.; Weber, W. A.; Bander, N. H.; Scher, H. I.; Morris, M. J.; Larson, S. M.
Article Title:	89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer
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:	adult; clinical article; human tissue; aged; unclassified drug; drug tolerability; advanced cancer; dose response; drug safety; comparative study; radiation dose; positron emission tomography; continuous infusion; pathology; chill; prostate cancer; liver; prostate specific membrane antigen; rigor; karnofsky performance status; isotope labeling; dosimetry; prostate biopsy; radiopharmaceutical agent; drug clearance; drug half life; radioimmunotherapy; bone scintiscanning; whole body pet; radioisotope distribution; whole body scintiscanning; clearance; j591 antibody; metastatic prostate cancer; human; male; article; 89zr-huj591; monoclonal antibody j591 zr 89
Journal Title:	European Journal of Nuclear Medicine and Molecular Imaging
Volume:	41
Issue:	11
ISSN:	1619-7070
Publisher:	Springer
Date Published:	2014-11-01
Start Page:	2093
End Page:	2105
Language:	English
DOI:	10.1007/s00259-014-2830-7
PROVIDER:	scopus
PUBMED:	25143071
PMCID:	PMC4404641
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84919950141&partnerID=40&md5=804092a8c5d630d1b7179d593dc94476
Notes:	Export Date: 2 February 2015 -- Source: Scopus