HERPET- A Novel PET Imaging Study of HER2 in Breast Cancer

This mechanistic study will be the first study to assess the efficacy of \[18F\]GE-226 to target HER2 expression in patients with metastatic breast cancer. The study will establish the pharmacokinetics of \[18F\]GE-226 and the optimum time-point for performing static scans in this patient population.

Objectives

Primary:

* To determine the uptake in tumour lesions and normal tissue of \[18F\]GE-226 and compare the difference between patients with HER2 positive and HER2 negative lesions. Uptake will be quantified by semi-quantitative (SUV, AUC) and fully quantitative parameters (Ki in the case of irreversible uptake, and binding potential in the case of reversible uptake)
* To determine the optimal imaging time point for \[18F\]GE-226

Secondary:

* To determine the safety and toxicity of \[18F\]GE-226 PET in humans
* To determine if \[18F\]GE-226 can distinguish between HER2 amplified and HER2 non-amplified breast tumours
* To determine the metabolism of \[18F\]GE-226 in human subjects

Exploratory:

• To explore circulating biomarkers that may be related to \[18F\]GE-226 uptake and to investigate if treatment modulates \[18F\]GE-226

Endpoints

Secondary:

* Safety and toxicity of \[18F\]GE-226 measured by adverse events from administration of \[18F\]GE-226 injection throughout the study period, and clinically significant changes from baseline measurements in serum biochemistry, haematology, coagulation, immunology, urinalysis, vital signs, ECG, injection site and physical examination findings.
* The association between \[18F\]GE-226 tumour uptake and standard HER2 pathological testing (HER2 amplified and HER2 non-amplified breast tumours)
* Proportion of metabolised \[18F\]GE-226 at scheduled time-points compared to baseline
* Normal tissue uptake of \[18F\]GE-226 will be quantified in the appropriate regions depending on the field of view.

Exploratory:

• To perform preliminary biodistribution analysis, to compare \[18F\]GE- 226 uptake to \[18F\]FDG uptake in tumour lesion

Eligibility Criteria:
Inclusion Criteria:

1. Female patients with a histological diagnosis of breast cancer with known HER2 status ((8 positive and 8 negative).
2. Written informed consent prior to admission in the study.
3. Target lesion diameter of ≥15mm that has not been previously irradiated.
4. Female patients aged ≥ 18 years of age.
5. For all patients: histologically confirmed locally advanced/metastatic breast cancer with a biopsy within the last 12 months confirming HER2 status by either immunohistochemistry (IHC), Silver In Situ Hybridization (SISH) or Fluorescent In Situ Hybridization (FISH).
6. ECOG performance status 0-2
7. Negative urine pregnancy test (within 2 hours prior to injection of imaging agent) in women of child bearing age and willingness to use contraception (barrier, abstinence, non-hormonal) for 3 weeks after injection of \[18F\]GE-226
8. Life expectancy \> 3 months
9. Adequate organ function as defined by

   * Hb≥10g/L
   * WBC≥3.0 x 109/L
   * PLT≥80 x 109/L
   * Serum creatinine ≤1.4mg/dl
   * SGOT and SGPT ≤2 x ULN
   * Total bilirubin ≤ 2 x ULN or 3.0 mg/dl in patients with Gilbert's syndrome
10. Patients must have been appropriately staged using FDG-PET within 42 days of study entry and additional imaging according to local standard of care

Exclusion Criteria:

1. Pregnant or lactating women.
2. History of cardiac disease (myocardial infarction, arrhythmias requiring therapy, symptomatic valvular disease, cardiomyopathy, or pericarditis).
3. Evidence of significant medical condition or laboratory finding which, in the opinion of the Investigator, makes it undesirable for the patient to participate in the trial.
4. Participants with severe claustrophobia or who are unable to lie flat or fit into the scanner (≥350 lbs (160 Kg)).
5. Prior use within 14 days of enrolment or concurrent therapy with any other investigational agent.
6. Patients classified as radiation workers
7. Patients on therapeutic doses of anticoagulants, or with a raised prothrombin time