title: Construction and in vitro/in vivo targeting of PSMA-targeted nanoscale microbubbles in prostate cancer.
abstract: BACKGROUND
  Prostate-specific membrane antigen (PSMA) is a highly specific biological marker and treatment target for prostate cancer. So ultrasound molecular imaging using PSMA antibody-loaded targeted nanoscale microbubbles (MBs) may contribute to the early diagnosis of prostate cancer.
  
  
  METHODS
  PSMA monoclonal antibody-loaded targeted nanoscale MBs were prepared using biotin-avidin technology. Antibody binding was evaluated with immunofluorescence. Using MKN45 gastric cancer cells as controls, the targeting capability of the targeted MBs was observed in prostate cancer cells (LNCaP and C4-2) under optical microscope. Contrast enhancement was monitored by an ultrasound system in C4-2, LNCaP, and MKN45 transplanted tumors in nude mice. The arrival time, time to peak, peak intensity, and duration of contrast enhancement of targeted and blank nanoscale MBs were compared and analyzed.
  
  
  RESULTS
  Targeted PSMA monoclonal antibody-loaded nanoscale MBs were successfully synthesized. These MBs were stable and could specifically bind to LNCaP and C4-2 cells in vitro but did not bind to MKN45 cells. There were significant differences in peak intensity and duration of contrast enhancement between targeted and blank nanoscale MBs in both transplanted prostate tumors (P < 0.05). Among the three types of transplanted tumors with targeted nanoscale MBs, the peak intensity was significantly higher in prostate tumors (LNCaP and C4-2) than in gastric tumors (MKN45) (P < 0.05).
  
  
  CONCLUSIONS
  PSMA monoclonal antibody-loaded targeted nanoscale MBs can target and bind to prostate cancer cells specifically and allow for obvious contrast enhancement in vivo. Therefore, this study lays a foundation for early diagnosis and targeted therapy for prostate cancer.
authors.affiliation: Department of Urology, Daping Hospital, Institute of Surgery Research, Third Military Medical University, Chongqing, China.
authors.forename: Luofu
authors.initials: L
authors.lastname: Wang
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.forename: Yanli
authors.initials: Y
authors.lastname: Guo
authors.forename: Haipeng
authors.initials: H
authors.lastname: Tong
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Fan
authors.forename: Jun
authors.initials: J
authors.lastname: Ding
authors.forename: Haiyun
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000378:metabolism; D043425:Glutamate Carboxypeptidase II / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles; D053758:Nanoparticles; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D021381:Protein Transport / Q000276:immunology
chemical_list: D003287:Contrast Media; D008562:Membrane Glycoproteins; D043425:Glutamate Carboxypeptidase II; C579805:PSMA protein, mouse