title: [¹⁸F]fluorothymidine-positron emission tomography in patients with locally advanced breast cancer under bevacizumab treatment: usefulness of different quantitative methods of tumor proliferation.
abstract: OBJECTIVE
  To investigate quantitative methods of tumor proliferation using 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) PET in patients with breast cancer (BC), studied before and after one bevacizumab administration, and to correlate the [(18)F]FLT-PET uptake with the Ki67 index.
  
  
  METHODS
  Thirty patients with newly diagnosed, untreated BC underwent a [(18)F]FLT-PET before and 14 days after bevacizumab treatment. A dynamic scan centered over the tumor began simultaneously with the injection of [(18)F]FLT (385 ± 56 MBq). Image derived input functions were obtained using regions of interest drawn on the left ventricle (LV) and descending aorta (DA). Metabolite corrected blood curves were used as input functions to obtain the kinetic Ki constant using the Patlak graphical analysis (time interval 10-60 min after injection). Maximum SUV values were derived for the intervals 40-60 min (SUV40) and 50-60 min (SUV50). PET parameters were correlated with the Ki67 index obtained staining tumor biopsies.
  
  
  RESULTS
  [(18)F]FLT uptake parameters decreased significantly (p<0.001) after treatment: SUV50=3.09 ± 1.21 vs 2.22 ± 0.96; SUV40=3.00 ± 1.18 vs 2.14 ± 0.95, Ki_LV(10-3)=52[22-116] vs 38[13-80] and Ki_DA(10-3)=49[15-129] vs 33[11-98]. Consistency interclass correlation coefficients within SUV and within Ki were high. Changes of SUV50 and Ki_DA between baseline PET and after one bevacizumab dose PET correlated with changes in Ki67 index (r-Pearson=0.35 and 0.26, p=0.06 and 0.16, respectively).
  
  
  CONCLUSIONS
  [(18)F]FLT-PET is useful to demonstrate proliferative changes after a dose of bevacizumab in patients with BC. Quantification of tumor proliferation by means of SUV and Ki has shown similar results, but SUV50 obtained better results. A correlation between [(18)F]FLT changes and Ki67 index was observed.
authors: Servicio de Medicina Nuclear, Clínica Universidad de Navarra, Pamplona, Spain. Electronic address: jmmartic@uanv.es.
authors: J M
authors: JM
authors: Marti-Climent
authors: Servicio de Medicina Nuclear, Clínica Universidad de Navarra, Pamplona, Spain.
authors: I
authors: I
authors: Dominguez-Prado
authors: Servicio de Medicina Nuclear, Clínica Universidad de Navarra, Pamplona, Spain.
authors: M J
authors: MJ
authors: Garcia-Velloso
authors: Departamento de Oncología Médica, Clínica Universidad de Navarra, Pamplona, Spain.
authors: V
authors: V
authors: Boni
authors: Servicio de Medicina Nuclear, Clínica Universidad de Navarra, Pamplona, Spain.
authors: I
authors: I
authors: Peñuelas
authors: Departamento de Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad de Navarra, Pamplona, Spain.
authors: I
authors: I
authors: Toledo
authors: Servicio de Medicina Nuclear, Clínica Universidad de Navarra, Pamplona, Spain.
authors: J A
authors: JA
authors: Richter
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology*; D049109:Cell Proliferation; D015224:Dideoxynucleosides; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography / Q000379:methods; D011446:Prospective Studies
chemical_list: D020533:Angiogenesis Inhibitors; D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; D000068258:Bevacizumab; C002854:alovudine
keywords: Angiogenesis; Angiogénesis; Bevacizumab; Breast cancer; Cáncer de mama; FLT; Fluorothymidine; Fluortimidina; PET