title: Imaging androgen receptor signaling with a radiotracer targeting free prostate-specific antigen.
abstract: Despite intense efforts to develop radiotracers to detect cancers or monitor treatment response, few are widely used as a result of challenges with demonstrating clear clinical use. We reasoned that a radiotracer targeting a validated clinical biomarker could more clearly assess the advantages of imaging cancer. The virtues and shortcomings of measuring secreted prostate-specific antigen (PSA), an androgen receptor (AR) target gene, in patients with prostate cancer are well documented, making it a logical candidate for assessing whether a radiotracer can reveal new (and useful) information beyond that conferred by serum PSA. Therefore, we developed (89)Zr-labeled 5A10, a novel radiotracer that targets "free" PSA. (89)Zr-5A10 localizes in an AR-dependent manner in vivo to models of castration-resistant prostate cancer, a disease state in which serum PSA may not reflect clinical outcomes. Finally, we demonstrate that (89)Zr-5A10 can detect osseous prostate cancer lesions, a context where bone scans fail to discriminate malignant and nonmalignant signals.
  
  
  CONCLUSIONS
  This report establishes that AR-dependent changes in PSA expression levels can be quantitatively measured at tumor lesions using a radiotracer that can be rapidly translated for human application and advances a new paradigm for radiotracer development that may more clearly highlight the unique virtues of an imaging biomarker.
authors.affiliation: Department of Surgery, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ulmert
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Evans
authors.forename: Jason P
authors.initials: JP
authors.lastname: Holland
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Rice
authors.forename: John
authors.initials: J
authors.lastname: Wongvipat
authors.forename: Kim
authors.initials: K
authors.lastname: Pettersson
authors.forename: Per-Anders
authors.initials: PA
authors.lastname: Abrahamsson
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.forename: Hans
authors.initials: H
authors.lastname: Lilja
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sawyers
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods; D009919:Orchiectomy; D049268:Positron-Emission Tomography; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy; D011849:Radioactive Tracers; D011868:Radioisotopes / Q000008:administration & dosage; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction; D014057:Tomography, X-Ray Computed; D015040:Zirconium / Q000008:administration & dosage
chemical_list: D011849:Radioactive Tracers; D011868:Radioisotopes; D011944:Receptors, Androgen; D015040:Zirconium; D017430:Prostate-Specific Antigen