Cu-64-SAR-Bombesin PET-CT imaging in the staging of ER+/PR+/HER2-metastatic breast cancer: Safety, dosimetry, and feasibility in a phase I trial.

3092 Background: Breast cancers are most frequently oestrogen receptor (ER) and progesterone receptor (PR) positive and 18F-Fluorodeoxyglucose PET-CT (FDG) used in conventional staging of breast cancer has lower sensitivity for these subtypes. Gastrin releasing peptide receptors (GRPR) are a potential alternative diagnostic and theranostic target for ER+/PR+ breast cancers due to their overexpression of GRPR. This phase 1 study aims to assess the safety and potential of the novel radiotracer 64Cu-Sarcophagine(SAR)-Bombesin (BBN) in the re-staging of recurrent metastatic ER+/PR+/human epidermal growth factor 2 negative (HER2-) breast cancer. Methods: Patients with confirmed recurrent or primary metastatic ER+/PR+/HER2- breast cancer undergoing staging prior to a new treatment underwent 64Cu-SAR-BBN PET-CT with imaging at 1, 3 and 24 hours post-injection. Bloods and vital signs were acquired for patients at baseline, 1, 3 and 24 hours post-injection timepoints, and electrocardiogram (ECG) performed 1 hour pre and 1 hour post injection. Blood tracer-clearance and dosimetry was performed. GRPR receptor status was assessed in 4/7 patients from metastatic-site biopsy samples. Staging of the patients was assessed by conventional imaging (FDG, bone scan and diagnostic CT) within 3 weeks of 64Cu-SAR-BBN imaging. All PET scans were assessed visually, and quantitatively using MIM Software. Results: 9 patients were enrolled. 7/9 patients underwent all imaging modalities, while 2/9 did not undergo BBN imaging. 1/7 patient who underwent all imaging had de- novo metastatic ER+/PR+/Her 2- breast cancer and 6/7 recurrent metastatic disease. 2/7 had lobular subtype. There were no adverse events reported, and ECG, vitals and haematological, biochemical and coagulation markers remained unchanged. All 7 patients were positive on conventional imaging, while 6/7 were positive on FDG. BBN was positive in 5/7 patients. Both BBN negative patients had disease identified on FDG. Conversely, 1 patient was BBN positive but FDG negative. 4/7 patients were BBN positive and FDG positive. In these 4 patients, mean SUVmax was higher for BBN than FDG (15 vs. 12). In classical lobular subtype (2/7), BBN was highly avid compared to FDG (SUV max 20 vs 11, and 20 vs <3) and with a higher tumor volume compared to FDG (2034 vs 504, and 634 mL vs FDG negative). Conclusions: 64Cu-SAR-Bombesin is a novel tracer which appears safe and may have a diagnostic and theranostic role in patients with metastatic ER+/PR+/HER2- breast cancer, particularly lobular subtype. Further evaluation appears warranted.