title: ⁸⁹Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer.
abstract: OBJECTIVE
  Given the bone tropism of prostate cancer, conventional imaging modalities poorly identify or quantify metastatic disease. (89)Zr-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 (89)Zr-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 (89)Zr-huJ591 immuno-PET imaging was analyzed and dosimetry was estimated using MIRD techniques. Initial assessment of lesion targeting of (89)Zr-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 (89)Zr-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 (89)Zr-huJ591, while the remaining 11 lesions were (89)Zr-huJ591 positive. Two biopsy-positive nodal lesions were noted only on (89)Zr-huJ591 study, while the conventional imaging modality was negative.
  
  
  CONCLUSIONS
  (89)Zr-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.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, pandit-n@mskcc.org.
authors.forename: Neeta
authors.initials: N
authors.lastname: Pandit-Taskar
authors.forename: Joseph A
authors.initials: JA
authors.lastname: O'Donoghue
authors.forename: Volkan
authors.initials: V
authors.lastname: Beylergil
authors.forename: Serge
authors.initials: S
authors.lastname: Lyashchenko
authors.forename: Shutian
authors.initials: S
authors.lastname: Ruan
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Solomon
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Durack
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Carrasquillo
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lefkowitz
authors.forename: Mithat
authors.initials: M
authors.lastname: Gonen
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Jason P
authors.initials: JP
authors.lastname: Holland
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Cheal
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Osborne
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Loda
authors.forename: Peter M
authors.initials: PM
authors.lastname: Smith-Jones
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Weber
authors.forename: Neil H
authors.initials: NH
authors.lastname: Bander
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D011829:Radiation Dosage; D011868:Radioisotopes; D015040:Zirconium
chemical_list: D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D015040:Zirconium