title: Indium 111-labeled J591 anti-PSMA antibody for vascular targeted imaging in progressive solid tumors.
abstract: BACKGROUND
  J591 is a monoclonal antibody that targets the external domain of the prostate-specific membrane antigen (PSMA). Besides prostate cancer cells, it also targets the neovasculature of non-prostate solid tumors. We provide an analysis of the antibody mass-dose dependency of lesion uptake and normal tissue retention, together with an assessment of lesion detectability using (111)In-J591 imaging, compared with conventional imaging in patients with a variety of solid tumors.
  
  
  METHODS
  Twenty patients in six cohorts received fixed amounts (5, 10, 20, 40, 60, and 100 mg) of J591 in a phase I trial. A maximum of four administrations per patient was given, with each administration separated by 3 weeks. All antibody administrations included 370 MBq (10 mCi) of (111)In labeled to 2 mg of J591 via the chelating agent DOTA. Three whole body (WB) gamma camera scans with at least one SPECT scan, along with multiple WB count-rate measurements and blood samples, were obtained for all patients. The effect of escalating antibody mass on lesion uptake and normal tissue retention was evaluated using lesion, liver, serum, and WB residence times and ratios thereof for each treatment cycle. Lesion detectability using (111)In-J591 imaging was compared to the standard imaging on a lesion-by-lesion basis.
  
  
  RESULTS
  A total of 170 lesions in 20 patients were detected by standard or (111)In-J591 imaging. (111)In-J591 targeted both skeletal and soft tissue diseases in all tumor types. (111)In-J591 imaging identified 74% (20/27) of skeletal lesions, 53% (18/34) of nodes, and 64% (70/109) of other soft tissue/organ lesions. There was increasing (111)In-J591 uptake in lesions with increasing antibody mass-dose, coupled with decreasing retention in the liver for increments up to 20 mg, and no significant change at higher antibody mass.
  
  
  CONCLUSIONS
  Radiolabeled J591 antibody has potential as a targeting agent for solid tumor vasculature and lesion detection. Bone and soft tissue lesions arising from tumors of diverse origin were targeted by the anti-PSMA antibody J591. For the detection of lesions in these tumors by J591 antibody scans, an antibody mass of 20 mg is adequate. The optimal time of imaging is 5 to 7 days post-injection.
authors.affiliation: Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 USA ; Department of Radiology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065 USA.
authors.forename: Neeta
authors.initials: N
authors.lastname: Pandit-Taskar
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: O'Donoghue
authors.affiliation: Nuclear Medicine Service, Department of Radiology, Columbia Presbyterian Medical Center, 630 West 168th Street, New York, NY 10032 USA.
authors.forename: Chaitanya R
authors.initials: CR
authors.lastname: Divgi
authors.affiliation: Nuclear Medicine Service, Department of Radiology, Columbia Presbyterian Medical Center, 630 West 168th Street, New York, NY 10032 USA.
authors.forename: Eze A
authors.initials: EA
authors.lastname: Wills
authors.affiliation: Nuclear Medicine Service, Department of Radiology, Columbia Presbyterian Medical Center, 630 West 168th Street, New York, NY 10032 USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Schwartz
authors.affiliation: Department of Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 USA.
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
authors.affiliation: Department of Radiology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065 USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Smith-Jones
authors.affiliation: Department of Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065 USA.
authors.forename: Neil H
authors.initials: NH
authors.lastname: Bander
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 USA ; Department of Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065 USA.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.affiliation: Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 USA ; Department of Radiology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065 USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 USA ; Department of Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065 USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
keywords: Biodistribution; J591 antibody; Lesion detectability; Neovasculature; Solid tumor