Clinical Application of 18F-3'-Fluoro-3'-Deoxy-L-thymidine (18F-FLT) Positron Emission Tomography (PET) in Lung Tumors

Lung cancer has become a leading cause of cancer death in Taiwan. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) using has been found to be effective in diagnosing, staging, and restaging primary non-small cell lung cancer (NSCLC). However, 18F-FDG is not tumor specific. It may also show increased uptake in benign tumors and tissue with inflammatory cells, such as macrophages and fibroblast. Therefore, the ability of 18F-FDG PET for characterizing lung nodule remains a challenge, especially in Taiwan where tuberculosis is still prevalent. Recently, 18F-3'-fluoro-3'-deoxy-L-thymidine (18F-FLT), a radiolabeled analog of thymidine, has been synthesized for imaging tumor cell proliferation in vivo. The tracer is trapped within the cytosol after being monophosphorylated by thymidine kinase-1 (TK-1), a principle enzyme in the salvage pathway of DNA synthesis. It has been demonstrated in cell culture, animal models and clinical studies that the accumulation of 18F-FLT is dependent on the presence of TK-1 and therefore is closely associated with cellular proliferation. Malignant lung lesions revealed significant 18F-FLT accumulation while benign lung tumors showed no 18F-FLT uptake. Therefore, 18F-FLT PET may be more accurate than 18F-FDG PET in differentiating benign from malignant pulmonary lesions. In addition, the correlation between 18F-FLT uptake and cellular proliferation hints the usefulness of 18F-FLT PET for monitoring treatment response with cytostatic anticancer drugs. In the meantime, the cyclotron and hot lab facility in National Taiwan University Hospital (NTUH) has developed 18F-FLT successfully. After careful quality assurance and animal experiments, it is now ready to perform clinical studies on human beings. We thus design this prospective 3-year project 1. To evaluate the usefulness of 18F-FLT PET and 18F-FDG PET in differentiating benign from malignant pulmonary nodules in Taiwan where tuberculosis is still prevalent. 2. To assess the usefulness of 18F-FLT PET in early prediction of therapeutic response of platinum-based chemotherapies or EGFR inhibitors for NSCLC patients. 3. To correlate 18F-FLT uptake with EGFR mutation status, therapeutic response and survival for NSCLC patients.