title: Biological basis of [¹¹C]choline-positron emission tomography in patients with breast cancer: comparison with [¹⁸F]fluorothymidine positron emission tomography.
abstract: OBJECTIVE
  The biological significance of [¹¹C]choline (CHO) uptake in human tumours is unclear and probably linked to choline kinase-α (CHKα) expression and cell proliferation. We directly compared CHO with [¹⁸F]fluorothymidine (FLT), an imaging biomarker of proliferation, by positron emission tomography (PET) in patients with breast cancer to investigate whether cell proliferation is an important determinant of CHO uptake. Furthermore, we evaluated CHKα and the Ki67-labelling index (LIKi67) in tumour biopsies.
  
  
  METHODS
  Sequential CHO-PET and FLT-PET within the same imaging session were performed in 21 patients with oestrogen receptor (ER)-positive breast cancer (28 lesions). Average and maximum CHO standardized uptake values (SUV) at 60 min: SUV60,av, and SUV60,max, and the rate constant of net irreversible uptake, Ki, were compared with FLT uptake at 60 min: SUV60,av and SUV60,max. Biopsies were stained for CHKα and LIKi67 in eight cases.
  
  
  RESULTS
  Tumours were equally visible on CHO-PET and FLT-PET imaging. Tumour CHO-PET strongly correlated with FLT imaging variables (Pearson's r=0.83; P<0.0001 for CHO-SUV60,max vs. FLT-SUV60,max). A statistically significant association was found between CHO-PET variables and categorical scores of cytoplasmic CHKα intensity and between FLT-PET and LIKi67 (P<0.05, one-way analysis of variance).
  
  
  CONCLUSIONS
  Choline metabolism and proliferation as assessed by PET were correlated in ER-positive breast cancer, indicating that high CHO uptake is a measure of cellular proliferation in this setting. CHO uptake was also found to be related to cytoplasmic CHKα expression.
authors.affiliation: Department of Oncology, Imperial College London, London, UK.
authors.forename: Kaiyumars B
authors.initials: KB
authors.lastname: Contractor
authors.forename: Laura M
authors.initials: LM
authors.lastname: Kenny
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.forename: Amarnath
authors.initials: A
authors.lastname: Challapalli
authors.forename: Adil
authors.initials: A
authors.lastname: Al-Nahhas
authors.forename: Carlo
authors.initials: C
authors.lastname: Palmieri
authors.forename: Sami
authors.initials: S
authors.lastname: Shousha
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Katy
authors.initials: K
authors.lastname: Hogben
authors.forename: Quang
authors.initials: Q
authors.lastname: De Nguyen
authors.forename: Raul Charles
authors.initials: RC
authors.lastname: Coombes
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000473:pathology; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D002250:Carbon Radioisotopes; D049109:Cell Proliferation; D002794:Choline; D002797:Choline Kinase / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D019394:Ki-67 Antigen / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals
chemical_list: D002250:Carbon Radioisotopes; D019394:Ki-67 Antigen; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C517212:CHKA protein, human; D002797:Choline Kinase; D002794:Choline