Fluorocholine PET/MR in Breast Cancer

Use of Imaging Markers by Fluorocholine PET/MR to Predict Molecular Subtypes and Clinical Outcomes of Breast Cancer: A Pilot Study

Objectives:

Our study is conducted to use the pre-treatment Fluorocholine (FCH) Positron emission tomography/magnetic resonance (PET/MR) imaging in breast cancer patients, to investigate whether the conventional PET/MR imaging markers (maximum standardized uptake value [SUVmax], MR spectroscopy-derived choline analysis, dynamic contrast-enhanced MRI, apparent diffusion coefficient [ADC] analysis), and FCH PET/MR radiomic features, deep learning (DL) analysis are associated with molecular subtypes, clinical outcomes, treatment response, survival, and which parameters are more accurate for predictive purposes.

Primary study purposes:

-To investigate whether the pre-treatment FCH PET/MR imaging parameters are associated with molecular subtypes of breast cancers, and to evaluate the diagnostic performance for predictive purposes.

Secondary study purposes:

-To investigate whether the pre-treatment FCH PET/MR imaging parameters are associated with the factors related to clinical outcomes (histologic grade, prognosis) and to analyze which parameters are more accurate for predictive purposes.

Test drug:

Name: 18F- Fluorocholine (18F-FCH) Dosage form: N-([18F]fluoromethyl)-2-hydroxy-N,N-dimethylethan-1-aminium Strength: 3-5 MBq/kg per patient (5-6 mCi/mL at time of injection (TOI)) Dosage and administration: Intravenous injection.fluoromethyl

Selection criteria:

1. Women aged 25-75 years old.
2. Women diagnosed with breast cancer by pathological diagnosis from a core biopsy within 3 months and who will receive neoadjuvant chemotherapy (NAC) before surgery; or women with pathologically proven breast cancer within 3 months and who will receive operation (without pre-operative neoadjuvant chemotherapy).
3. Women whose Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and life expectancy at least 3 months.

Study steps / procedures:

1. The study participants will receive pre-treatment whole-body PET/MR and breast PET/MR examinations.
2. The whole-body PET/MR:

(1). The participant will undergo NPO for at least 6 hours before the examination.

(2). After intravenous injection of 5-6 mCi 18F- Fluorodeoxyglucose (FDG), the participant will rest for approximately 60 minutes, followed by a 20-25-minute whole-body PET/MR examination. FDG is a commercially available PET tracer approved for clinical diagnosis.

3. PET/MR of the breast:

1. . The participant will undergo fasting (nothing by mouth, nil per os [NPO]) for at least 6 hours before the examination.
2. . After intravenous injection of 5-6 mCi/mL (at TOI) 18F-Fluorocholine (FCH), the study participant will take a 45-60-minute bed rest and then undergo a breast PET/MR with prone position. The breast PET/MR will take about 30-35 minutes. The intravenous injection of MRI contrast media will be performed during the examination (MRI-contrast agent, Dotarem [Gadoteric acid, Guerbet, France] is commercialized and routinely used in MRI examination). The dosage of MRI contrast media ranges from 10-15 cc according to various body weight (0.1mmol/Kg).

4. The whole-body FDG PET/MR, and the breast FCH PET/MR will be performed on different days (interval of at least 2 days).

5. The study results will be interpreted by board certified diagnostic radiologists and nuclear medicine physicians, and relayed to the patient's physicians for reference of clinical management.

6. The radiation dose (effective dose equivalent, EDE) of a whole-body FDG PET/MR measures about 6.6 millisievert [mSv], the EDE of a FCH breast PET/MR measures about 3.85 mSv, totally about 10.45 mSv, which is relatively equivalent to that of a chest CT scan (without and with contrast, 10.8 mSv), resulting in a very low estimated risk of secondary cancer (about 5/10000 to 7/10000). Most of the radioactivity from FDG and FCH will decay naturally, and only a minimal portion will be excreted through the urinary and hepatobiliary systems.

Inclusion Criteria:

• Women aged 25-75 years old.
• Women diagnosed with breast cancer by pathological diagnosis from a core biopsy within 3 months and who will receive neoadjuvant chemotherapy (NAC) before surgery; or women with pathologically proven breast cancer within 3 months and who will receive operation (without pre-operative neoadjuvant chemotherapy).
• Women whose ECOG performance status between 0-2 and life expectancy at least 3 months.

Exclusion Criteria:

• Women who are unable to cooperate with the examinations
• Women who are pregnant, lactating or are planning to be pregnant
• Women with estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or acute renal failure within 3 months, past history of renal dialysis.
• Past history of claustrophobia
• Past history of anaphylactoid reactions to MRI contrast agents or PET tracer agents.
• Women with cardiac pacemaker, aneurysmal clip, mechanical valve replacement, recently applied coronary artery stent (within 3 months).
• Past history of breast cancer or other malignancy within 5 years.
• Women who underwent chemotherapy within a year.
• Women who are not suitable to join the study according to the assessment by investigators.