title: Measurement of circulating cell-free DNA in relation to 18F-fluorocholine PET/CT imaging in chemotherapy-treated advanced prostate cancer.
abstract: OBJECTIVE
  To examine the effects of chemotherapy on circulating cell-free DNA (cfDNA) composition in relation to investigational whole-body measurement of tumor activity by fluorine-18 fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) in hormone-refractory prostate cancer (HRPC).
  
  
  METHODS
  Serial FCH PET/CT scans were performed in eight patients with HRPC receiving docetaxel-based chemotherapy. Corresponding serial cfDNA samples were characterized by microfluidic electrophoresis, quantified by real-time PCR, and compared with PET/CT results. Promoter methylation of two prostate cancer-associated genes, GSTP1 and RARB2, was assessed by methylation-specific PCR of bisulfite-converted cfDNA.
  
  
  RESULTS
  Plasma cfDNA concentrations increased significantly from 13.3 ng/mL at baseline to 46.8 ng/mL and 50.9 ng/mL after one and three treatment cycles, respectively (p= 0.001). GSTP1 and/or RARB2 promoter methylation was identified in all pretreatment samples. The appearance of large (200 bp-10.4 kb) cfDNA fragments was noted in posttreatment samples along with loss of methylation at GSTP1 and/or RARB2. Tumor activity on PET/CT correlated with cfDNA concentration (r=-0.50, p= 0.01). Patients meeting criteria for PET tumor response had significantly lower pretreatment cfDNA levels than those who did not (8.0 vs. 16.4 ng/mL, p= 0.03).
  
  
  CONCLUSIONS
  Chemotherapy is associated with significant changes in plasma cfDNA content and FCH PET/CT-detected tumor activity. These interrelated measures are potential candidate markers of therapeutic response in HRPC.
authors.affiliation: The University of Hawaii Cancer Center, Honolulu, HI, USA. skwee@queens.org
authors.forename: Sandi
authors.initials: S
authors.lastname: Kwee
authors.forename: Min-Ae
authors.initials: MA
authors.lastname: Song
authors.forename: Iona
authors.initials: I
authors.lastname: Cheng
authors.forename: Lenora
authors.initials: L
authors.lastname: Loo
authors.forename: Maarit
authors.initials: M
authors.lastname: Tiirikainen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002794:Choline / Q000031:analogs & derivatives*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood*; D000077143:Docetaxel; D046209:Electrophoresis, Microchip; D005819:Genetic Markers; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006254:Hawaii; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D019275:Radiopharmaceuticals; D060888:Real-Time Polymerase Chain Reaction; D018168:Receptors, Retinoic Acid / Q000235:genetics; D043823:Taxoids / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D051598:Whole Body Imaging
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005819:Genetic Markers; C533416:RARB2 protein, human; D019275:Radiopharmaceuticals; D018168:Receptors, Retinoic Acid; D043823:Taxoids; D000077143:Docetaxel; C514960:fluorocholine; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D002794:Choline