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

NCT ID: NCT01089894

Last Updated: 2010-03-19

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 90 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2011-07-31

Brief 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.

Detailed Description

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.

Conditions

Lung Cancer

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

18F-FLT 1

18F-FLT in differentiating benign from malignant pulmonary nodules

No interventions assigned to this group

18F-FLT 2

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.)

No interventions assigned to this group

18F-FLT 3

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.)

No interventions assigned to this group

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

National Taiwan University Hospital

Principal Investigators

Ruoh-Fang Yen, M.D PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

National Taiwan University Hospital

Taipei, Taiwan, Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Ruoh-Fang Yen, M.D., Ph.D.

Role: CONTACT

rfyen@ntu.edu.tw

886-2-23123456 ext. 65581

Facility Contacts

Ruoh-Fang Yen, M.D., Ph.D.

Role: primary

rfyen@ntu.edu.tw

886-2-23123456 ext. 65581

Other Identifiers

200712071R

Identifier Type: -

Identifier Source: org_study_id