Clinical Application of 18F-FLT 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.
Observational Model: Case-Only, Time Perspective: Prospective
Ruoh-Fang Yen, M.D PhD
National Taiwan University Hospital
Taiwan: Department of Health