title: Multispectral autofluorescence imaging for detection of cervical lesions: A preclinical study.
abstract: OBJECTIVE
  The aim of this study was to develop a novel optical imaging system for detecting protoporphyrin IX (PpIX) autofluorescence, to prove that PpIX autofluorescence is as useful as 5-aminolevulinic acid (5-ALA)-induced fluorescence for detecting and localizing cervical cancer, and to monitor the change in PpIX autofluorescence or induced PpIX fluorescence before, during, and after photodynamic therapy (PDT).
  
  
  METHODS
  TC-1 cells - highly tumorigenic cells immortalized using human papillomavirus type 16 proteins E6 and E7 - were subcutaneously grafted into the thighs of nude mice. The suspected tumor tissues were visualized using autofluorescence imaging and induced fluorescence imaging under 5-ALA administration. When the 5-ALA-induced PpIX was sufficiently accumulated in tumor tissues, PDT was performed using a 635-nm laser. We observed the change in fluorescence intensity during PDT. For 3 weeks after PDT, we monitored tumor remission by using white-light imaging and fluorescence imaging.
  
  
  RESULTS
  The transplanted cells were visualized by PpIX autofluorescence, which was induced by heme synthesis. After 5-ALA administration, PpIX could be targeted by using PDT, which decreased PpIX autofluorescence. Photobleaching is useful for monitoring PDT dosimetry and for determining the photodynamic response to therapy.
  
  
  CONCLUSIONS
  PpIX autofluorescence clearly differentiated the tumor from adjacent normal tissues. The results of PpIX autofluorescence imaging and 5-ALA-induced fluorescence imaging were identical. PpIX autofluorescence imaging is a simple and cost-effective cervical cancer screening method that could be performed during or after PDT to ensure effective treatment or remission as a change in fluorescence intensity can be observed in real time without a blinding effect.
authors.affiliation: Korea Electrotechnology Research Institute, Seoul, Korea.|Department of Obstetrics and Gynecology, Catholic Research Institutes of Medical Science, The Catholic University of Korea, Seoul, Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Bae
authors.affiliation: Korea Electrotechnology Research Institute, Seoul, Korea.
authors.forename: Dae-Sic
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Korea Electrotechnology Research Institute, Seoul, Korea.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Berezin
authors.affiliation: Korea Electrotechnology Research Institute, Seoul, Korea.|SNUH Biomedical Research Institute, Seoul, Korea.
authors.forename: Uk
authors.initials: U
authors.lastname: Kang
authors.affiliation: Department of Obstetrics and Gynecology, Catholic Research Institutes of Medical Science, The Catholic University of Korea, Seoul, Korea.
authors.forename: Keun-Ho
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000622:Aminolevulinic Acid / Q000493:pharmacokinetics*; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D052162:Human papillomavirus 16; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D010778:Photochemotherapy; D011524:Protoporphyrins / Q000493:pharmacokinetics*; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy
chemical_list: D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: 5-aminolevulinic acid; autofluorescence; cervical cancer; multispectral; photodynamic therapy