clinical application of 18f-3'-fluoro-3'-deoxy-l-thymidine (18f-flt) positron emission tomography (pet) in lung tumors

Conditions: Lung Cancer

Summary: the ability of 18f-fdg pet for characterizing lung nodule remains a challenge, especially in taiwan where tuberculosis is still prevalent. 18f-3'-fluoro-3'-deoxy-l-thymidine (18f-flt), a radiolabeled analog of thymidine, can be 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 closely associated with cellular proliferation. 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. 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.

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.

Eligibility criteria:
inclusion criteria: 18f-flt 1: 1. indeterminate pulmonary nodule(s) 2. has been scheduled an 18f-fdg pet for characterization of their indeterminate pulmonary nodule(s) 3. consent to perform an additional 18f-flt pet 4. will receive biopsy or surgery for the pulmonary nodule(s) 18f-flt 2: 1. has pathological proved nsclc 2. is staged as inoperable advanced nsclc 3. has been scheduled to receive platinum-based chemotherapy 4. consents to received 18f-flt pet studies before, at the day before initiation of 2nd cycle of therapy or at 7 days after completion of therapy 18f-flt 3: 1. has pathological proved nsclc 2. is staged as inoperable advanced nsclc 3. has been scheduled to receive egfr tyrosine kinase inhibitor therapy 4. consents to received 18f-flt pet studies before, at the 2nd day or at the 7th day of therapy 5. consents to undergo egfr mutation analysis exclusion criteria: 1. patients with other known malignancies 2. age under 18 years 3. hematological parameters: wbc \< 3000/l or platelet \< 75,000/l (who toxicity criteria of grade 1) 4. abnormal liver function: ast or alt \> 78u/l (who toxicity criteria of grade 1) 5. renal function: creatinine \> 2.0 mg/dl (who toxicity criteria of grade 1)

Keywords: 18f-flt pet non-small cell lung cancer cell proliferation therapeutic response 18f-3'-fluoro-3'-deoxy-l-thymidine (18f-flt)