title: First-in-Human Imaging with 89Zr-Df-IAB2M Anti-PSMA Minibody in Patients with Metastatic Prostate Cancer: Pharmacokinetics, Biodistribution, Dosimetry, and Lesion Uptake.
abstract: We conducted a phase I dose-escalation study with89Zr-desferrioxamine-IAB2M (89Zr-IAB2M), an anti-prostate-specific membrane antigen minibody, in patients with metastatic prostate cancer.
  
  
  METHODS
  Patients received 185 MBq (5 mCi) of89Zr-IAB2M and Df-IAB2M at total mass doses of 10 (n = 6), 20 (n = 6), and 50 mg (n = 6). Whole-body and serum clearance, normal-organ and lesion uptake, and radiation absorbed dose were estimated, and the effect of mass escalation was analyzed.
  
  
  RESULTS
  Eighteen patients were injected and scanned without side effects. Whole-body clearance was monoexponential, with a median biologic half-life of 215 h, whereas serum clearance showed biexponential kinetics, with a median biologic half-life of 3.7 (12.3%/L) and 33.8 h (17.9%/L). The radiation absorbed dose estimates were 1.67, 1.36, and 0.32 mGy/MBq to liver, kidney, and marrow, respectively, with an effective dose of 0.41 mSv/MBq (1.5 rem/mCi). Both skeletal and nodal lesions were detected with89Zr-IAB2M, most visualized by 48-h imaging.
  
  
  CONCLUSIONS
  89Zr-IAB2M is safe and demonstrates favorable biodistribution and kinetics for targeting metastatic prostate cancer. Imaging with 10 mg of minibody mass provides optimal biodistribution, and imaging at 48 h after injection provides good lesion visualization. Assessment of lesion targeting is being studied in detail in an expansion cohort.
authors: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York pandit-n@mskcc.org.|Department of Radiology, Weill Cornell Medical College, New York, New York.
authors: Neeta
authors: N
authors: Pandit-Taskar
authors: Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Joseph A
authors: JA
authors: O'Donoghue
authors: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Shutian
authors: S
authors: Ruan
authors: Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Serge K
authors: SK
authors: Lyashchenko
authors: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Radiology, Weill Cornell Medical College, New York, New York.
authors: Jorge A
authors: JA
authors: Carrasquillo
authors: Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Glenn
authors: G
authors: Heller
authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Danny F
authors: DF
authors: Martinez
authors: Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Sarah M
authors: SM
authors: Cheal
authors: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Radiology, Weill Cornell Medical College, New York, New York.|Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, New York.|Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Jason S
authors: JS
authors: Lewis
authors: Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Martin
authors: M
authors: Fleisher
authors: ImaginAb, Inc., Inglewood, California; and.
authors: Jennifer S
authors: JS
authors: Keppler
authors: ImaginAb, Inc., Inglewood, California; and.
authors: Robert E
authors: RE
authors: Reiter
authors: ImaginAb, Inc., Inglewood, California; and.
authors: Anna M
authors: AM
authors: Wu
authors: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Radiology, Weill Cornell Medical College, New York, New York.
authors: Wolfgang A
authors: WA
authors: Weber
authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: Howard I
authors: HI
authors: Scher
authors: 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 Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Steven M
authors: SM
authors: Larson
authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: Michael J
authors: MJ
authors: Morris
mesh_terms: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology*; D001692:Biological Transport; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism / Q000493:pharmacokinetics*; D043425:Glutamate Carboxypeptidase II / Q000276:immunology*; D006207:Half-Life; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology* / Q000378:metabolism; D007136:Immunoglobulins / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009362:Neoplasm Metastasis; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D011829:Radiation Dosage; D011874:Radiometry; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D002352:Carrier Proteins; D007128:Immunoglobulin Fragments; D007136:Immunoglobulins; C081296:Minibody (WT); C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: 89Zr- IAB2M; PSMA; dosimetry; minibody; prostate cancer imaging