Abstract PD6-09: Herpet study- PET imaging of HER2 expression in breast cancer using the novel Affibody tracer [18F]GE-226, a first in patient study
Authors: Kenny Laura M. , Gopalakrishnan Gosala S. , Barwick Tara D. , Vaja Vijay , McDevitt S. Hope , Punjani Robert , Patel Neva H. , Ramakrishnan Rathi , Patel Naina R. , Johnston Stephen , Mansi Janine , Cook Gary J. , Gilbert Fiona J. , Aigbirhio Franklin I. , Hiscock Duncan , Aboagye Eric O. 
Published: February 2021

Abstract
Background 20% of breast cancers have over-expression of the human epidermal growth factor receptor-2 (HER2), which is an adverse prognostic factor and used to guide therapy selection. At present HER2 expression can only be determined using biopsy material which is then analysed using immunohistochemistry or fluorescence in situ hybridisation. GE-226 is a radiolabelled Affibody® tracer which binds to the HER2 receptor with high affinity at a different epitope than trastuzumab. Heterogeneous expression does exist but the impact this has on treatment response has not been well assessed. A non-invasive method for determining HER2 expression could have several advantages and help select appropriate therapy for patients.
Trial DesignPatients with locally advanced or metastatic breast cancer were recruited and scanned for 65 mins after iv injection of 200MBq (mean activity injected for each patient 198 MBq (range 164-219MBq), mean radiochemical purity 94.6%) of tracer, with one dynamic bed position, and then a half-body scan was performed. Blood sampling was used to measure metabolism of the tracer. Safety was recorded. HER2-extracellular domain (ECD) domain was measured in blood. The original accrual target was 16 patients. Tumoural uptake was quantified by semi-quantitative and fully quantitative parameters in HER2 positive and HER2 negative tumours.
ResultsThirteen patients were recruited. Scans were well tolerated. There were no serious adverse events. GE-226 was metabolised into a single metabolite in the liver. 96.8 % parent remained at 60 minutes post injection. There was a significant difference between HER2 positive and HER2 negative tumoural uptake of tracer as measured by SUVmean and SUVmax (p&lt;0.05). Comparing HER2 positive to HER2 negative cases, there was also a significant difference between tumour to normal tissue uptake ratios (p&lt;0.05). Heterogeneous uptake was observed in the same patient. Tumoural uptake increased over time. Uptake in salivary glands and the thyroid gland was noted. In one patient GE-226 was able to differentiate between lymphadenopathy due to sarcoidosis and cancer and was superior to FDG which had shown widespread uptake in the same patient.
Conclusions[18F]GE-226 imaging is well tolerated and shows promise for imaging of HER2 positive breast cancer. Further studies with this agent are now planned.
Citation Format: Laura M. Kenny, Gosala S. Gopalakrishnan, Tara D. Barwick, Vijay Vaja, S. Hope McDevitt, Robert Punjani, Neva H. Patel, Rathi Ramakrishnan, Naina R. Patel, Stephen Johnston, Janine Mansi, Gary J. Cook, Fiona J. Gilbert, Franklin I. Aigbirhio, Duncan Hiscock, Eric O. Aboagye. Herpet study- PET imaging of HER2 expression in breast cancer using the novel Affibody tracer [18F]GE-226, a first in patient study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD6-09.