PET STUDIES IN PATIENTS WITH LIVER METASTASES RECEIVING CHEMOTHERAPY

摘要

While 5-fluorouracil (FU) has been in use for chemotherapy in patients with metastatic colorectal cancer for several years, little is known about its pharmacokinetics in metastases. Positron emission tomography (PET) studies were performed with ~(15)O-water and ~(18)F-FU to evaluate tumour perfusion and FU pharmacokinetics. The evaluation included 50 patients (78 metastases). Five 1 min images were acquired following intravenous injection of ~(15)O-water (1184-3700 MBq). Then ~(18)F-FU was given, together with 500 mg unlabelled FU in a 12 min infusion, and data were acquired for 2 h (12 × 2, 7 × 5 and 6 × 10 min). The iteratively reconstructed cross-sections were evaluated using the regions of interest technique and time activity curves were calculated for the lesions, the normal liver parenchyma and the aorta. PET images were used 8 min after the end of the 12 min FU infusion to quantify FU transport into the metastases. Late images 120 min after onset of the infusion were used to evaluate the cytostatically active fraction. Tumour perfusion was evaluated on the basis of the 5 min standardized uptake value (SUV) obtained from the ~(15)O-water study. In selected patients double tracer studies were performed using systemic as well as regional tracer applications. It was possible to compare the PET results obtained prior to the first chemotherapeutic cycle with the tumour growth rate during treatment of 25 lesions. The maximum liver activity (11.3 SUV) was achieved 30 min (mean value) after the onset of ~(18)F-FU infusion. The mean ~(18)F-FU accumulation in metastases was one third the concentrations measured in normal liver parenchyma 120 min post-injection. No significant correlation was noted for tumour perfusion as measured by ~(15)O-water and FU transport (20 min SUV). Furthermore, no correlation was found between tumour perfusion and FU retention (120 min SUV). Regional tracer application resulted in higher ~(18)F-FU retention in 59% of the metastases. Cluster analysis was used to evaluate the correlation between tumour perfusion, FU transport and FU retention in 53 liver metastases. Two clusters were noted. While a linear correlation (r = 0.61) existed in 30 metastases (cluster I) between tumour perfusion and FU transport, no correlation was observed in the second cluster (cluster II), comprising 10 of 40 metastases. Furthermore, highrnFU retention (>2.0 SUV) was observed in 7 out of 10 metastases in Cluster II, but only in 1 out of 30 lesions in cluster I. A high correlation was noted between the PET ~(18)F-FU concentration measurements and the tumour growth rate during chemotherapy. Therefore, PET studies prior to FU treatment can be used to predict therapy outcome.