64Cu-SAR-Bombesin PET-CT Imaging in the Staging of Estrogen/Progesterone Receptor Positive, HER2 Negative Metastatic Breast Cancer Patients: Safety, Dosimetry and Feasibility in a Phase I Trial

Keith Wong; Gemma Sheehan-Dare; Andrew Nguyen; Bao Ho; Victor Liu; Jonathan Lee; Lauren Brown; Rachel Dear; Lyn Chan; Shikha Sharma; Alessandra Malaroda; Isabelle Smith; Elgene Lim; Louise Emmett

doi:10.3390/ph15070772

⁶⁴Cu-SAR-Bombesin PET-CT Imaging in the Staging of Estrogen/Progesterone Receptor Positive, HER2 Negative Metastatic Breast Cancer Patients: Safety, Dosimetry and Feasibility in a Phase I Trial

Pharmaceuticals (Basel). 2022 Jun 22;15(7):772. doi: 10.3390/ph15070772.

Authors

Keith Wong¹, Gemma Sheehan-Dare¹, Andrew Nguyen^{1

2}, Bao Ho^{1

2}, Victor Liu¹, Jonathan Lee¹, Lauren Brown³, Rachel Dear³, Lyn Chan^{1

2}, Shikha Sharma¹, Alessandra Malaroda¹, Isabelle Smith¹, Elgene Lim^{2

3

4}, Louise Emmett^{1

2

3}

Affiliations

¹ Department of Theranostics and Nuclear Medicine, St Vincent's Hospital, 390 Victoria Street, Sydney, NSW 2010, Australia.
² St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia.
³ The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW 2010, Australia.
⁴ Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.

Abstract

Breast cancers are most frequently oestrogen receptor (ER) and progesterone receptor (PR) positive and [18F]Fluorodeoxyglucose PET-CT (FDG) has lower sensitivity for these subtypes. The gastrin-releasing peptide receptor (GRPR) is overexpressed in ER+/PR+ breast cancers. This study assessed the safety and potential of [64Cu]Cu-Sarcophagine (SAR)-Bombesin PET/CT (BBN) in re-staging metastatic ER+/PR+/human epidermal growth-factor-2-negative (HER2-) breast cancer. Seven patients with metastatic ER+/PR+/HER2- breast cancer undergoing staging underwent [64Cu]Cu-SAR-BBN PET-CT. Bloods, vital signs and electrocardiogram, blood tracer-clearance and dosimetry were undertaken. GRPR status was assessed in available metastatic biopsy samples. Staging with conventional imaging ([18F]FDG, bone scan and diagnostic CT) was within 3 weeks of [64Cu]Cu-SAR-BBN PET/CT. PET scans were assessed visually and quantitatively. Seven patients underwent imaging. One of the seven had de-novo metastatic breast cancer and six of the seven recurrent metastatic disease. Two of the seven had lobular subtype. No adverse events were reported. All seven patients were positive on conventional imaging (six of seven on FDG). [64Cu]Cu-SAR-BBN imaging was positive in five of the seven. Both [64Cu]Cu-SAR-BBN-negative patients had disease identified on [18F]FDG. One patient was [64Cu]Cu-SAR-BBN positive/[18F]FDG negative. Four of seven patients were [64Cu]Cu-SAR-BBN positive/[18F]FDG positive. In these four, mean SUVmax was higher for [64Cu]Cu-SAR-BBN than [18F]FDG (SUVmax 15 vs. 12). In the classical lobular subtype (two of seven), [64Cu]Cu-SAR-BBN was more avid compared to [18F]FDG (SUVmax 20 vs. 11, and 20 vs. <3). Dosimetry calculations estimated whole-body effective dose for 200 MBq of [64Cu]Cu-SAR-BBN to be 1.9 mSv. [64Cu]Cu-SAR-BBN PET/CT appears safe and may have diagnostic value in metastatic ER+/PR+/HER2- breast cancer, particularly the lobular subtype. Further evaluation is warranted.

Keywords: PET; SAR-BBN; bombesin; breast cancer; copper 64; staging.

Grants and funding

n/a/Clarity Pharmaceuticals