title: Effects of capecitabine treatment on the uptake of thymidine analogs using exploratory PET imaging agents:18F-FAU,18F-FMAU, and18F-FLT.
abstract: BACKGROUND
  A principal goal for the use of positron emission tomography (PET) in oncology is for real-time evaluation of tumor response to chemotherapy. Given that many contemporary anti-neoplastic agents function by impairing cellular proliferation, it is of interest to develop imaging modalities to monitor these pathways. Here we examined the effect of capecitabine on the uptake of thymidine analogs used with PET: 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT), 1-(2'-deoxy-2'-[18F]fluoro-β-D-arabinofuranosyl) thymidine (18F-FMAU), and 1-(2'-deoxy-2'-[18F]fluoro-β-D-arabinofuranosyl) uracil (18F-FAU) in patients with advanced cancer.
  
  
  METHODS
  Fifteen patients were imaged, five with each imaging agent. Patients had been previously diagnosed with breast, colorectal, gastric, and esophageal cancers and had not received therapy for at least 4 weeks prior to the first scan, and had not been treated with any prior fluoropyrimidines. Subjects were imaged within a week before the start of capecitabine and on the second day of treatment, after the third dose of capecitabine. Tracer uptake was quantified by mean standard uptake value (SUVmean) and using kinetic analysis.
  
  
  RESULTS
  Patients imaged with18F-FLT showed variable changes in retention and two patients exhibited an increase in SUVmeanof 172.3 and 89.9 %, while the other patients had changes ranging from +19.4 to -25.4 %. The average change in18F-FMAU retention was 0.2 % (range -24.4 to 23.1) and18F-FAU was -10.2 % (range -40.3 to 19.2). Observed changes correlated strongly with SUVmaxbut not kinetic measurements.
  
  
  CONCLUSIONS
  This pilot study demonstrates that patients treated with capecitabine can produce a marked increase in18F-FLT retention in some patients, which will require further study to determine if this flare is predictive of therapeutic response.18F-FAU and18F-FMAU showed little change, on average, after treatment.
authors.affiliation: Cancer Biology Graduate Program, Wayne State University, Detroit, MI, 48201, USA.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: McHugh
authors.affiliation: Karmanos Cancer Institute and Oncology, Wayne State University, 4100 John R., HW04HO, Detroit, MI, 48201, USA.
authors.forename: Jawana M
authors.initials: JM
authors.lastname: Lawhorn-Crews
authors.affiliation: Karmanos Cancer Institute and Oncology, Wayne State University, 4100 John R., HW04HO, Detroit, MI, 48201, USA.
authors.forename: Dipenkumar
authors.initials: D
authors.lastname: Modi
authors.affiliation: Karmanos Cancer Institute and Oncology, Wayne State University, 4100 John R., HW04HO, Detroit, MI, 48201, USA.
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Douglas
authors.affiliation: Cancer Biology Graduate Program, Wayne State University, Detroit, MI, 48201, USA.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Jones
authors.affiliation: Radiology, Wayne State University, Detroit, MI, 48201, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Mangner
authors.affiliation: National Cancer Institute, Bethesda, MD, 20892, USA.
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Collins
authors.affiliation: Karmanos Cancer Institute and Oncology, Wayne State University, 4100 John R., HW04HO, Detroit, MI, 48201, USA. shieldsa@karmanos.org.
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Shields
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000069287:Capecitabine / Q000009:adverse effects* / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
chemical_list: C558662:1-(2'-deoxy-2'-fluoro-1-arabinofuranosyl)-5-uracil; D000964:Antimetabolites, Antineoplastic; D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; D000069287:Capecitabine; C034935:clevudine; C002854:alovudine
keywords: Capecitabine; FAU; FLT; FMAU; Oncology; PET