Abstract P4-01-17: Molecular imaging and quantification of HER-2 status in metastatic breast cancer by using 68Ga-ABY-025/PET-CT

Abstract

Abstract Background: Molecular imaging, in particular, positron emission tomography (PET) provides unique possibility to non-invasively quantify the biomarkers. A small peptide, ABY-025, is targeting a unique epitope of the HER2-receptor and can be labeled with 111In or 68Ga. It is non-competitive with current antibody-targeted epitopes and is approximately 25 times smaller than an antibody and posses superior pharmacokinetics as imaging agent. We have earlier reported promising results of lesion visualization and determination of HER2 status by 111In-ABY-025/SPECT-CT in seven patients with metastatic breast cancer (MBC). As PET-CT provides superior possibilities for quantification and allows for imaging with shorter time frames, we now investigate 68Ga-ABY-025 in HER2-positive and HER2-negative MBC patients in a prospective study. The influence of the administered amount of ABY-025 on the discrimination between HER2-positive and HER2-negative metastases as well as detection rate and image contrast is investigated. The HER2 status changes will be followed at disease progression. We report here promising data on the first three patients. Patients and methods: The study considers twenty patients in two cohorts. Of the first 10 patients, 4 should have HER2-negative MBC and 6 patients HER2-positive disease. Metastases were localized by 18F-FDG/PET-CT prior HER2 imaging. Each patient (two HER2-positive and one HER-negative) underwent two subsequent examinations. First, 68Ga-ABY-025 PET/CT (ABY-025: 75±14 μg) was performed with dynamic acquisition during 0-45 minutes and static images after 1, 2 and 4 hours. The procedure was repeated after one week with a higher dose of 68Ga-ABY-025 (ABY-025: 445±10 μg) to identify the optimal dosage for the discrimination between HER2-positive and HER2-negative metastases. Blood levels of radioactivity, anti-ABY-025-antibodies, shed serum HER2 and toxicity markers were evaluated. Biopsies were taken to verify the HER2 status of the lesions. The second cohort of 10 patients (all with HER2-positive disease), will have their primary PET-CT with the optimal dose of 68Ga-ABY-025 and will, as the HER-positive from the first cohort, have a follow-up 68Ga-ABY-025 PET/CT after disease progression or, at latest, after 9 months. Results: The imaging agent was well tolerated by the patients without adverse events. The rapid blood clearance and normal tissue wash out allowed high contrast HER2 images within a few hours. The HER2 status was confirmed by histological analysis of biopsies. In one patient with HER2-negative primary tumor, imaging suggested a HER2-positive liver metastasis. The change of HER2 expression was verified with analysis of the corresponding biopsy. This finding resulted in the change of the treatment management. Preliminary validation suggests the preference of high dose ABY-025 in terms of image contrast and detection. The study is ongoing and more patients will be reported Conclusion: Preliminary results indicate strong potential of 68Ga-ABY-025 PET/CT for discriminating HER2-positive versus HER2-negative metastatic breast cancer, regardless of ongoing HER2-targeted antibody treatment. The method introduces rapid whole-body receptor mapping of primary tumor and metastases in a single examination. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-17.