Differential super( 18)F-FDG and super( 18)F-FLT Uptake on Serial PET/CT Imaging Before and During Definitive Chemoradiation for Non-Small Cell Lung Cancer

We aimed to prospectively observe cellular metabolism and proliferation in patients with non-small-cell lung cancer (NSCLC) during radical chemoradiation therapy using serial PET/CT with super( 18)F-FDG and 3'-deoxy- 3'- super( 18)F-fluorothymidine ( F-FLT). Twenty patients with stage I-III NSCLC and candidates for radical chemoradiation therapy (60 Gy in 30 fractions over 6 wk) were recruited. super( 18)F-FDG and super( 18)F-FLT PET/CT were performed at baseline and during therapy (weeks 2 and 4). Tumor response was assessed semiquantitatively and using visual response criteria. The median and range for primary tumor volume (cm super( 3)) at baseline on super( 18)FFDG were 28 and 2-241, respectively, and on super( 18)F-FLT 31 and 2-184, respectively. At week 2, super( 18)F-FDG was 26 (range, 2-164), and super( 18)F-FLT was 11 (range, 0-111). At week 4, super( 18)F-FDG was 19 (1-147), and super( 18)F-FLT was 7 (0-48). The median and range of maximum standardized uptake value (SUV sub( max)) at baseline on super( 18)F-FDG were 14 and 4-31, respectively, and on super( 18)F-FLT 6 and 2-12, respectively. Week 2 super( 18)F-FDG median SUV sub( max) was 10 (2-31), and super( 18)F-FLT median SUV sub( max) was 3 (1-15); week 4 super( 18)F-FDG median SUV sub( max) was 10 (2-15), and super( 18)F-FLT median SUV sub( max) was 2 (2-9). There was fair agreement between visual tumor response on super( 18)F-FDG and super( 18)F-FLT during therapy (Cohen's unweighted statistic, 0.27 at week 2 and 0.355 at week 4). Cerebral metastases were detected on 1 baseline super( 18)F-FLT scan, resulting in palliative management. Progressive disease was detected on week 2 scans in 3 patients, resulting in changes to radiation therapy (2 patients) and treatment intent (1 patient). This study demonstrates that super( 18)FFLT PET/CT is a more sensitive tracer of early treatment response than super( 18)FFDG PET/CT. The ability of these tracers to detect distinct biologic processes may lead to their use as biomarkers for personalized radiation therapy and prognosis in the future.