title: MRl of prostate cancer antigen expression for diagnosis and immunotherapy.
abstract: BACKGROUND
  Tumor antigen (TA)-targeted monoclonal antibody (mAb) immunotherapy can be effective for the treatment of a broad range of cancer etiologies; however, these approaches have demonstrated variable clinical efficacy for the treatment of patients with prostate cancer (PCa). An obstacle currently impeding translational progress has been the inability to quantify the mAb dose that reaches the tumor site and binds to the targeted TAs. The coupling of mAb to nanoparticle-based magnetic resonance imaging (MRI) probes should permit in vivo measurement of patient-specific biodistributions; these measurements could facilitate future development of novel dosimetry paradigms wherein mAb dose is titrated to optimize outcomes for individual patients.
  
  
  METHODS
  The prostate stem cell antigen (PSCA) is broadly expressed on the surface of prostate cancer (PCa) cells. Anti-human PSCA monoclonal antibodies (mAb 7F5) were bound to Au/Fe(3)O(4) (GoldMag) nanoparticles (mAb 7F5@GoldMag) to serve as PSCA-specific theragnostic MRI probe permitting visualization of mAb biodistribution in vivo. First, the antibody immobilization efficiency of the GoldMag particles and the efficacy for PSCA-specific binding was assessed. Next, PC-3 (prostate cancer with PSCA over-expression) and SMMC-7721 (hepatoma cells without PSCA expression) tumor-bearing mice were injected with mAb 7F5@GoldMag for MRI. MRI probe biodistributions were assessed at increasing time intervals post-infusion; therapy response was evaluated with serial tumor volume measurements.
  
  
  RESULTS
  Targeted binding of the mAb 7F5@GoldMag probes to PC-3 cells was verified using optical images and MRI; selective binding was not observed for SMMC-7721 tumors. The immunotherapeutic efficacy of the mAb 7F5@GoldMag in PC-3 tumor-bearing mice was verified with significant inhibition of tumor growth compared to untreated control animals.
  
  
  CONCLUSIONS
  Our promising results suggest the feasibility of using mAb 7F5@GoldMag probes as a novel paradigm for the detection and immunotherapeutic treatment of PCa. We optimistically anticipate that the approaches have the potential to be translated into the clinical settings.
authors: Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xian, China.
authors: Jing
authors: J
authors: Ren
authors: Fang
authors: F
authors: Wang
authors: Guangquan
authors: G
authors: Wei
authors: Yong
authors: Y
authors: Yang
authors: Ying
authors: Y
authors: Liu
authors: Mengqi
authors: M
authors: Wei
authors: Yi
authors: Y
authors: Huan
authors: Andrew C
authors: AC
authors: Larson
authors: Zhuoli
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D055910:Antibodies, Immobilized; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000737:chemistry; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006046:Gold / Q000737:chemistry; D006801:Humans; D007167:Immunotherapy; D008279:Magnetic Resonance Imaging; D008297:Male; D053768:Metal Nanoparticles; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*; D014018:Tissue Distribution
chemical_list: D055910:Antibodies, Immobilized; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D005290:Ferric Compounds; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; C000499:ferric oxide; D006046:Gold