Radiolabeled acetate PET in oncology imaging : studies on head and neck cancer, prostate cancer and normal distribution

Abstract: The use of positron emission tomography (PET) for imaging in oncology has grown rapidly in recent years. 2-[18F]-fluorodeoxyglucose (FDG) is the most common tracer of PET, although drawbacks exist. Radiolabeled 1-[11C]-acetate (C-AC) is a simple probe for evaluation of perfusion, anabolism (lipogenesis) and catabolism (oxidative metabolism) in all living tissues. This study explored the potential of AC PET in head and neck cancer, benign and malignant lymph nodes in prostate cancer and normal distribution.  In head and neck cancer, C-AC PET detected more primaries and lymph node metastases than FDG PET. The mean primary tumor volumes delineated by C-AC was 51% larger than that of FDG before radiotherapy (RT). Both FDG and C-AC PET tumor volumes must be carefully validated before used in clinical routine. Baseline tumor clearance rate (kmono) was higher in complete responders (CR) than that in partial responders (PR). kmono tended to correlate inversely with FDG SUV at baseline. Radiosensitive tumors might rely predominantly on oxidative metabolism for their biogenetic needs. kmono increased in PR during RT. The potential reversibility of impaired kmono in radioresistant tumors imply that treatment targeting the intermediary metabolism might improve the outcome. Tumor relative perfusion index (rF) and kmono were coupled in CR throughout the RT, but not in PR. Dynamic C-AC PET provides a new non-invasive method to simultaneously evaluate the tumor oxidative metabolism and perfusion which link the RT response in patients by a single tracer injection. In prostate cancer, elevated C-AC accumulation is common in benign inguinal lymph nodes, probably due to increased lipogenesis rather than lymphatic drainage. CT Hounsfield unit of benign nodes was lower than that of metastases, suggesting that density measurement using CT might improve the specificity of nodal staging of prostate cancer. A novel tracer 2-[18F]-fluoroacetate (F-AC) was synthesized and used for dynamic PET-CT imaging in animals. Compared with C-AC PET-CT, F-AC showed prolonged blood retention, no detectable trapping in myocardium and salivary glands, rapid excretion from liver to bile and urine and de-fluorination resulting in intensive skeletal activity. F-AC does not mimic the normal physiologic path of C-AC and appears to be of little use for assessment of perfusion, intermediary metabolism or lipogenesis.