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

Lung Cancer Clinical Trial

Official title:

Clinical Application of 18F-FLT PET in Lung Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01089894
• Other study ID #: 200712071R
• Status: Recruiting
• Phase: N/A
• First received: March 17, 2010
• Last updated: March 18, 2010
• Start date: August 2008
• Est. completion date: July 2011

Study information

• Verified date: March 2010
• Source: National Taiwan University Hospital
• Contact: Ruoh-Fang Yen, M.D., Ph.D.
• Phone: 886-2-23123456
• Email: rfyen[@]ntu.edu.tw
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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)

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Lung Cancer

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan,