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

Study Overview
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Brief Summary
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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 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. To assess the usefulness of 18F-FLT PET in early prediction of therapeutic response of platinum-based chemotherapies or EGFR inhibitors for NSCLC patients. To correlate 18F-FLT uptake with EGFR mutation status, therapeutic response and survival for NSCLC patients.

Detailed Description
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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 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. To assess the usefulness of 18F-FLT PET in early prediction of therapeutic response of platinum-based chemotherapies or EGFR inhibitors for NSCLC patients. To correlate 18F-FLT uptake with EGFR mutation status, therapeutic response and survival for NSCLC patients.

Official Title
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Clinical Application of 18F-FLT PET in Lung Tumors

Conditions
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Lung Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18F-FLT 1: indeterminate pulmonary nodule(s) has been scheduled an 18F-FDG PET for characterization of their indeterminate pulmonary nodule(s) consent to perform an additional 18F-FLT PET will receive biopsy or surgery for the pulmonary nodule(s) 18F-FLT 2: has pathological proved NSCLC is staged as inoperable advanced NSCLC has been scheduled to receive platinum-based chemotherapy 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: has pathological proved NSCLC is staged as inoperable advanced NSCLC has been scheduled to receive EGFR tyrosine kinase inhibitor therapy consents to received 18F-FLT PET studies before, at the 2nd day or at the 7th day of therapy consents to undergo EGFR mutation analysis Exclusion Criteria: Patients with other known malignancies Age under 18 years Hematological parameters: WBC < 3000/L or platelet < 75,000/L (WHO toxicity criteria of grade 1) Abnormal liver function: AST or ALT > 78U/L (WHO toxicity criteria of grade 1) Renal function: Creatinine > 2.0 mg/dl (WHO toxicity criteria of grade 1)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 18F-FLT 1<br>18F-FLT in differentiating benign from malignant pulmonary nodules | |
| 18F-FLT 2<br>18F-FLT in evaluating therapeutic response of platinum-based chemotherapy (The chemotherapeutic drugs used in the study are all approved by the Department of Health, Taiwan.) | |
| 18F-FLT 3<br>18F-FLT in evaluating therapeutic response of EGFR tyrosin kinase inhibitors (The target therapeutic drugs used in the study are all approved by the Department of Health, Taiwan.) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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18F-FLT, PET, non-small cell lung cancer, cell proliferation, therapeutic response, 18F-3'-fluoro-3'-deoxy-L-thymidine (18F-FLT)