title: A Phase I/II Study for Analytic Validation of 89Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer.
abstract: OBJECTIVE
  Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of (89)Zr-DFO-huJ591 ((89)Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared with conventional imaging modalities (CIM) and pathology.
  
  
  METHODS
  Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of (89)Zr-J591. Whole-body PET/CT scans were obtained, and images were analyzed for tumor visualization. Comparison was made to contemporaneously obtained bone scintigraphy and cross-sectional imaging on a lesion-by-lesion basis and with biopsies of metastatic sites.
  
  
  RESULTS
  Median standardized uptake value for (89)Zr-J591-positive bone lesions (n = 491) was 8.9 and for soft-tissue lesions (n = 90), it was 4.8 (P < 0.00003). (89)Zr-J591 detected 491 osseous sites compared with 339 by MDP and 90 soft-tissue lesions compared with 124 by computed tomography (CT). Compared with all CIMs combined, (89)Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 (89)Zr-J591-positive osseous sites and 14 of 16 (89)Zr-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of (89)Zr-J591 was 95.2% (20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions.
  
  
  CONCLUSIONS
  (89)Zr-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although (89)Zr-J591 had similar accuracy as individual CIMs. This study will provide benchmark data for comparing performance of proposed prostate-specific membrane antigen (PSMA) targeting agents for prostate cancer.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Radiology, Weill Cornell Medical College, New York, New York. pandit-n@mskcc.org.
authors.forename: Neeta
authors.initials: N
authors.lastname: Pandit-Taskar
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: O'Donoghue
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Durack
authors.affiliation: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York. Radiochemistry and Molecular Imaging Probe Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Serge K
authors.initials: SK
authors.lastname: Lyashchenko
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Cheal
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Volkan
authors.initials: V
authors.lastname: Beylergil
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lefkowitz
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Carrasquillo
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Danny F
authors.initials: DF
authors.lastname: Martinez
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Alex Mak
authors.initials: AM
authors.lastname: Fung
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Solomon
authors.affiliation: Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
authors.affiliation: Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.affiliation: Department of Pathology, Dana-Farber Cancer Institute; Brigham & Women's Hospital; and Broad Institute, Boston, Massachusetts.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: David M
authors.initials: DM
authors.lastname: Nanus
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Tagawa
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jarett L
authors.initials: JL
authors.lastname: Feldman
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Osborne
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, New York. Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York. Radiochemistry and Molecular Imaging Probe Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Weber
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Neil H
authors.initials: NH
authors.lastname: Bander
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Radiology, Weill Cornell Medical College, New York, New York. Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
mesh_terms: D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000175:diagnosis / Q000556:secondary; D006801:Humans; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012983:Soft Tissue Neoplasms / Q000175:diagnosis / Q000556:secondary
chemical_list: D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals