Biological basis of [11C]choline-positron emission tomography in patients with breast cancer: comparison with [18F]fluorothymidine positron emission tomography

Objective The biological significance of [C-11] choline (CHO) uptake in human tumours is unclear and probably linked to choline kinase-alpha (CHK alpha) expression and cell proliferation. We directly compared CHO with [F-18] 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 CHK alpha 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 CHKa 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 CHKa intensity and between FLT-PET and LIKi67 (P < 0.05, one-way analysis of variance). Conclusion 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 CHKa expression. Nucl Med Commun 32: 997-1004 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.