Human Epidermal Growth Factor Receptor 2 (HER2) PET Imaging of HER2-Low Breast Cancer with [68Ga]Ga-ABY-025: Results from a Pilot Study

Renske Altena; Siri Af Burén; August Blomgren; Emelie Karlsson; Antonios Tzortzakakis; Nikolai Brun; Mohammad M Moein; Emma Jussing; Fredrik Y Frejd; Jonas Bergh; Thuy A Tran; Johan Hartman; Rimma Axelsson

doi:10.2967/jnumed.123.266847

Human Epidermal Growth Factor Receptor 2 (HER2) PET Imaging of HER2-Low Breast Cancer with [⁶⁸Ga]Ga-ABY-025: Results from a Pilot Study

J Nucl Med. 2024 Mar 28:jnumed.123.266847. doi: 10.2967/jnumed.123.266847. Online ahead of print.

Authors

Renske Altena^{1

2}, Siri Af Burén^{3

4}, August Blomgren⁴, Emelie Karlsson², Antonios Tzortzakakis^{3

4}, Nikolai Brun⁵, Mohammad M Moein⁶, Emma Jussing^{2

6}, Fredrik Y Frejd^{5

7}, Jonas Bergh^{8

2}, Thuy A Tran^{2

6}, Johan Hartman^{2

9}, Rimma Axelsson^{4

10}

Affiliations

¹ Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Solna, Sweden; renske.altena@ki.se.
² Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
³ Division of Radiology, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
⁴ Medical Radiation Physics and Nuclear Medicine, Functional Unit of Nuclear Medicine, Karolinska University Hospital, Huddinge, Sweden.
⁵ Affibody AB, Solna, Sweden.
⁶ Department of Radiopharmacy, Karolinska University Hospital, Solna, Sweden.
⁷ Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
⁸ Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Solna, Sweden.
⁹ Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, Solna, Sweden; and.
¹⁰ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

PMID: 38548353
DOI: 10.2967/jnumed.123.266847

Abstract

Patients with HER2-low metastatic breast cancer (mBC), defined as an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification, may benefit from HER2 antibody-drug conjugates. Identifying suitable candidates is a clinical challenge because of spatial and temporal heterogeneity in HER2 expression and discrepancies in pathologic reporting. We aimed to investigate the feasibility and safety of HER2-specific PET imaging with [⁶⁸Ga]Ga-ABY-025 for visualization of HER2-low mBC. Methods: A prospective pilot study was done with 10 patients who had HER2-low mBC, as part of a phase 2 basket imaging study with [⁶⁸Ga]Ga-ABY-025 in HER2-expressing solid tumors. Patients were recruited at the Breast Clinic at the Karolinska University Hospital, Stockholm, Sweden. PET/CT images were acquired 3 h after injection of 200 MBq of [⁶⁸Ga]Ga-ABY-025. The SUV_max was used to quantify tracer uptake. Ultrasound-guided tumor biopsies were guided by results from the HER2 PET. The main outcome-the safety and feasibility of HER2 PET in patients with HER2-low mBC, measured the occurrence of possible procedure-related adverse events. Results: Ten patients with HER2-low mBC underwent [⁶⁸Ga]Ga-ABY-025 PET/CT with paired tumor biopsies. No adverse events occurred. In all patients, [⁶⁸Ga]Ga-ABY-025-avid lesions with substantial intra- and interindividual heterogeneity in tracer uptake were noted. In 8 of 10 patients with ABY-025-avid lesions, the HER2-low status of the corresponding lesions was confirmed by IHC or in situ hybridization. Two patients had an IHC score of 0 in the tumor biopsies:1 in a cutaneous lesion with a low SUV_max and 1 in a liver metastasis with a high SUV_max but a "cold" core. Conclusion: The visualization of HER2-low mBC with [⁶⁸Ga]Ga-ABY-025 PET/CT was feasible and safe. Areas of tracer uptake showed varying levels of HER2 expression on IHC. The observed intra- and interindividual heterogeneity in [⁶⁸Ga]Ga-ABY-025 uptake suggested that HER2 PET might be used as a tool for the noninvasive assessment of disease heterogeneity and has the potential to identify patients in whom HER2-targeted drugs can have a clinical benefit.

Keywords: HER2 PET; HER2-low breast cancer; [68Ga]Ga-ABY-025.