FDG and FMISO PET Hypoxia Evaluation in Cervical Cancer

PRIMARY OBJECTIVES:

I. Test the extent to which fluoromisonidazole F 18 ([^18F] FMISO) uptake predicts survival of patients undergoing therapy for newly diagnosed stage IB-IVB cervical cancer.

SECONDARY OBJECTIVES:

I. Test [^18F] FMISO tumor uptake as an independent predictor of response to therapy and that it provides additional predictive power over fludeoxyglucose F 18 ([^18F] FDG).

II. Test [^18F] FMISO tumor uptake as a predictor of response in a subgroup of patients receiving radiotherapy.

III. Test the relationship between [^18F] FMISO uptake in the primary tumor and the volume of the primary tumor estimated by CT scan.

IV. Test the reproducibility of [^18F] FMISO uptake in tumors by imaging the same patients on sequential days in a test-retest protocol.

V. Compare [^18F] FMISO PET or PET/CT scan with [^18F] FDG PET or PET/CT scan to test whether [^18F] FMISO is an independent predictor of treatment outcome.

OUTLINE:

Patients receive fluoromisonidazole F 18 ([^18F] FMISO) IV over 1 minute followed by PET scanning. Patients undergo a second [^18F] FMISO PET scan 4-8 weeks later. Patients who have not had a prior fludeoxyglucose F 18 ([^18F] FDG) PET scan as part of their routine clinical management undergo [^18F] FDG PET scanning at baseline. A subset of 10 patients undergo two [^18F] FMISO PET scans within a 48-hour period to evaluate the variability (test-retest) of this imaging measurement.

Patients response to therapy is followed periodically until time to disease progression or for 2 years.

Inclusion criteria

• Histologically confirmed squamous cell or adenocarcinoma of the uterine cervix
• Clinical stage IB-IVB by FIGO criteria

• Size of the primary tumor ≥ 2 cm as assessed by CT scan
• Measurable disease
• Scheduled to undergo radiotherapy, chemotherapy, or combined multimodality management
• No prior cervical cancer diagnosis
• No known brain metastases
• ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)
• Life expectancy > 12 months
• Not pregnant
• No nursing for 24 hours after fluoromisonidazole F 18 ([^18F] FMISO) PET scanning
• Negative pregnancy test
• Weight ≤ 400 lbs
• Sufficiently healthy to undergo cancer treatment
• Willing to undergo PET scanning with urinary bladder catheterization
• Leukocytes ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Total bilirubin normal
• AST/ALT ≤ 2.5 times normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• No serious medical co-morbidities that would preclude definitive local therapy
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to [^18F] FMISO
• No concurrent uncontrolled illness including, but not limited to, any of the following:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements.
• No prior surgery or radiotherapy for cervical cancer
• Other concurrent investigational agents allowed