BOA19
Evaluation of elevated choline metabolism in patients with endocrine resistant breast cancer using [11C]choline and [18F]fluorothymidine PET
Kaiyumars Contractor1, Laura Kenny1, Justin Stebbing2, Jie Jiang1, David Peston2, Sami Shousha2, Simak Ali1, Adil Al-Nahhas2, Jacqueline Lewis2, Dudley Sinnett2, Carlo Palmieri2, Charles Coombes1, Eric Aboagye1
1Imperial College, London, UK, 2Imperial College Healthcare NHS Trust, London, UK
Background
Transformation and progression of mammary epithelial cells is associated with enhanced choline metabolism. This phenotype is regulated in part by the Mitogen-activated-protein-kinase (MAPK) signalling cascade. The aim of this study was to assess, using imaging approaches, whether patients with endocrine resistant breast cancer had higher choline metabolism and MAPK activity.
Method
21 ER positive breast cancer patients (10 primary untreated; 11 metastatic after adjuvant endocrine therapy) underwent dual PET scanning with [11C]choline and [18F]fluorothymidine (FLT) to image tumour choline metabolism and proliferation, respectively. Tumours from these patients were immunostained for Ki67 and phosphorylated MAPK (pMAPK).Furthermore, a separate cohort of 30 archived paired primary versus metastatic breast tumour biopsies were analysed for pMAPK status.
Results
Choline uptake was higher in metastatic tumours (median Ki=12.8x10-4; range 1.0-31.9x10-4 ml plasma.ml-1 tissue.s-1) compared to the primary tumours (median Ki=7.2x10-4; range 1.1-17.6x10-4 ml plasma.ml-1 tissue.s-1); p=0.02. In contrast cell proliferation, measured by FLT was similar between the two groups. [11C]choline uptake (Ki) correlated well with tumour size (p=0.003, r=0.6); FLT uptake (SUV) correlated well with tumour grade (p=0.02, r=0.57) and Ki67 index (p=0.0019, r=0.86 respectively). pMAPK showed a trend of increased staining from primary to metastatic disease in 14/30 pairs although no correlation was seen between Ki [11C]choline and pMAPK in the limited cohort of patients imaged by PET.
Conclusion
[11C]choline uptake, but not cell proliferation, was higher in metastatic endocrine resistant breast cancer. A larger cohort of patient is required to assess the relationship between [11C]choline and pMAPK.
