title: Applications of immunoPET: using 124I-anti-PSCA A11 minibody for imaging disease progression and response to therapy in mouse xenograft models of prostate cancer.
abstract: OBJECTIVE
  Prostate stem cell antigen (PSCA) is highly expressed in local prostate cancers and prostate cancer bone metastases and its expression correlates with androgen receptor activation and a poor prognosis. In this study, we investigate the potential clinical applications of immunoPET with the anti-PSCA A11 minibody, an antibody fragment optimized for use as an imaging agent. We compare A11 minibody immunoPET to (18)F-Fluoride PET bone scans for detecting prostate cancer bone tumors and evaluate the ability of the A11 minibody to image tumor response to androgen deprivation.
  
  
  METHODS
  Osteoblastic, PSCA-expressing, LAPC-9 intratibial xenografts were imaged with serial (124)I-anti-PSCA A11 minibody immunoPET and (18)F-Fluoride bone scans. Mice bearing LAPC-9 subcutaneous xenografts were treated with either vehicle or MDV-3100 and imaged with A11 minibody immunoPET/CT scans pre- and posttreatment. Ex vivo flow cytometry measured the change in PSCA expression in response to androgen deprivation.
  
  
  RESULTS
  A11 minibody demonstrated improved sensitivity and specificity over (18)F-Fluoride bone scans for detecting LAPC-9 intratibial xenografts at all time points. LAPC-9 subcutaneous xenografts showed downregulation of PSCA when treated with MDV-3100 which A11 minibody immunoPET was able to detect in vivo.
  
  
  CONCLUSIONS
  A11 minibody immunoPET has the potential to improve the sensitivity and specificity of clinical prostate cancer metastasis detection over bone scans, which are the current clinical standard-of-care. A11 minibody immunoPET additionally has the potential to image the activity of the androgen signaling axis in vivo which may help evaluate the clinical response to androgen deprivation and the development of castration resistance.
authors.affiliation: Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Knowles
authors.affiliation: Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Tavaré
authors.affiliation: Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California.
authors.forename: Kirstin A
authors.initials: KA
authors.lastname: Zettlitz
authors.affiliation: Department of Surgery, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Rochefort
authors.affiliation: Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California.
authors.forename: Felix B
authors.initials: FB
authors.lastname: Salazar
authors.affiliation: Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California. Department of Urology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California.
authors.forename: Ziyue Karen
authors.initials: ZK
authors.lastname: Jiang
authors.affiliation: Department of Urology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Reiter
authors.affiliation: Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California. awu@mednet.ucla.edu.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wu
mesh_terms: D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001549:Benzamides; D004195:Disease Models, Animal; D018450:Disease Progression; D058851:GPI-Linked Proteins / Q000276:immunology; D064593:Heterografts; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D014018:Tissue Distribution; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: D000726:Androgen Antagonists; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D001549:Benzamides; D058851:GPI-Linked Proteins; D007128:Immunoglobulin Fragments; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D009570:Nitriles; C110843:PSCA protein, human; D010669:Phenylthiohydantoin; C540278:enzalutamide