Serial [18F]Thymidine (FLT)PET/CT as a Biomarker of Response in Pemetrexed Therapy for Non-Small Cell Lung Cancer

We will test the hypothesis that positron emission tomography (PET) imaging with the imaging
agent 18F-thymidine (FLT) can rapidly assess treatment response in patients with non-small
cell lung cancer (NSCLC). In particular, we hypothesize that FLT-PET imaging will offer the
potential of rapidly triaging therapy efficacy within hours to days following the start of
therapy start by non-invasively monitoring metabolic changes in the tumor, rather than the
conventional approach of waiting months for tumors to grow or shrink on computed tomography
(CT).

We propose two approaches to evaluate the potential of FLT-PET for assessment of response to
therapy in NSCLC. In the first, we will exploit a specific effect (the FLT "flare") induced
by pemetrexed, which is first-line chemotherapy for non-squamous NSCLC, to evaluate the
utility of FLT-PET to assess successful response to pemetrexed (PEM) therapy within 24 hours.
In the second approach, we will utilize FLT as a marker of cell proliferation, as has been
done in other cancers, to determine whether chemotherapy has produced a decrease in tumor
growth at 2 weeks after starting therapy. Since approximately 70% of patients will fail
PEM-based therapy, an imaging technique that could reliably detect PEM efficacy in hours to
days rather than months would save valuable time and allow for switch to a more effective
therapy.

Inclusion Criteria:

1. Adult patients, at least 18 years of age

2. Histologically confirmed non-small cell lung cancer with at least one site of disease
> 1 cm by at least one type of standard imaging (e.g. CT, chest x-ray, MRI)

3. Recommended to start systemic therapy which includes pemetrexed and a platinum-based
agent.

4. Participants must be informed of the investigational nature of this study and provide
written informed consent in accordance with institutional and federal guidelines prior
to study-specific procedures.

5. Participants must be willing and able to comply with scheduled visits and imaging
procedures in the opinion of the investigator or treating physician.

Exclusion Criteria:

1. Females who are pregnant or breast-feeding at the time of screening will not be
eligible for this study. Female participants of child-bearing potential will have a
urine pregnancy test at the time of the screening visit.

2. Patients with only a single site of primary lung cancer who have undergone or are
recommended to undergo radiation therapy to that site will not be eligible, the
inclusion of patients who may be undergoing radiation therapy to ancillary disease
sites may be allowed to enter the study at the discretion of the PI if it is not felt
to affect the ability to capture FLT information for at least one primary site of
disease.

3. Patients who have received chemotherapy within 2 weeks of enrollment will be excluded
from the study.

4. Patients who have undergone cancer surgery removing a significant portion of active
disease, in the opinion of an investigator, within 2 months prior to study enrollment
will be excluded.

5. Inability to tolerate imaging procedures in the opinion of the investigator or
treating physician

6. Serious or unstable medical or psychological conditions that, in the opinion of the
investigator would compromise the subject's safety or successful participation in the
study.

7. Unwilling or unable to provide informed consent