title: Noninvasive assessment of cell proliferation in ovarian cancer using [18F] 3'deoxy-3-fluorothymidine positron emission tomography/computed tomography imaging.
abstract: BACKGROUND
  Positron emission tomography (PET)/computed tomography (CT) imaging of suspected new and recurrent ovarian carcinoma was performed to assess the relationship between [(18)F] 3'deoxy-3'fluorothymidine ((18)FLT) uptake and histopathological tissue markers of cellular proliferation (Ki67) and thymidine kinase-1 (TK-1) expression.
  
  
  METHODS
  Six subjects were included in this pilot study. Subjects were injected with 5 mCi of (18)FLT prior to a planned surgery and then scanned on a GE Discovery-ST PET/CT scanner within an hour of injection. Regions of interest in tumor and control tissue were identified on the diagnostic CT scans and marked for later surgical biopsy. Surgery was performed within 2 days after the scan. At the time of surgery, the regions of interest identified on PET/CT were available to guide the surgeon to the tumor biopsy sites. Tissue from normal ovarian tissue control regions was also sampled. (18)FLT uptake in tumor and control tissue regions was calculated by measuring the maximum standardized uptake values (SUV(max)). The excised tumor and normal ovarian tissue control tissues were analyzed by immunohistochemical staining for Ki67 and CD34. TK-1 messenger RNA expression was measured by real-time polymerase chain reaction.
  
  
  RESULTS
  (18)FLT uptake (SUV(max)) was higher in malignant (mean 4.85/range 1.7-8.8) compared to benign (1.65/range 1.4-1.9) and normal ovarian control tissue (1.12/range 0.6-1.5). Mitotic index, as determined by Ki67 staining, was higher in malignant (18.89/range 11.97-27.19) compared to benign (0.59/range 0.23-0.95) and control tissue (0.45/range 0.06-1.20). TK-1 expression was also higher in malignant (35.52/range 5.21-106.62) compared to benign (8.71/range 4.74-12.67) and control tissue (9.79/range 0.85-39.46). An increasing trend between (18)FLT uptake and Ki67 mitotic index is seen in malignant tissue CD 34 staining between malignant, benign and control tissues was not qualitatively different.
  
  
  CONCLUSIONS
  An increasing trend between (18)FLT uptake and Ki67 mitotic index is seen in malignant tissue. Additional studies will determine whether (18)FLT PET/CT is specific enough to distinguish between cancerous and noncancerous cells and to assess its role in ovarian carcinoma patient management.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Services, Division of Gynecologic Oncology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Richard
authors.forename: Badreddine
authors.initials: B
authors.lastname: Bencherif
authors.forename: Robert P
authors.initials: RP
authors.lastname: Edwards
authors.forename: Esther
authors.initials: E
authors.lastname: Elishaev
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Krivak
authors.forename: James M
authors.initials: JM
authors.lastname: Mountz
authors.forename: Julie A
authors.initials: JA
authors.lastname: DeLoia
mesh_terms: D000368:Aged; D001692:Biological Transport; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D015224:Dideoxynucleosides / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D012008:Recurrence; D013937:Thymidine Kinase / Q000235:genetics; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor; D015224:Dideoxynucleosides; D019394:Ki-67 Antigen; D013937:Thymidine Kinase; C092717:thymidine kinase 1; C002854:alovudine