Forsøksdyr: The early-stage loco-regional recurrence of basal-like breast cancer imaging by using [18F] c-Met

Godkjenningsdato 19.03.2018

The c-Met (proto oncogene) is a receptor tyrosine kinase activated by the ligand hepatocyte growth factor (HGF). The HGF/c-Met signaling axis has been described as a promoter of cancer cell growth, angiogenesis, invasion and metastasis. Overexpression of c-Met is associated with poor prognosis and a more malignant tumor phenotype . Several c-Met inhibitors are currently under evaluation in clinical trials, either as stand-alone therapies or in concomitant treatment . c-Met is overexpressed in various solid tumors , including breast cancer (BC), with higher expression in Basal-like Breast Cancer (BLBC) than in other intrinsic cancer subtypes . BLBC, which accounts for up to 15% of all BCs, exhibits a high rate of loco-regional recurrence after initial therapy.

Although treatment of localized disease has improved over the past decades, up to 45% of BC
patients suffer a local, regional or systemic relapse within 8 years after initial therapy . While systemic relapse in the form of distant metastasis is still regarded as incurable according to current treatment guidelines, loco-regional recurrence of BC should be treated with curative intention. Treatment success crucially depends on the earliest possible diagnosis, before chest wall involvement or further organ invasion prevents any form of aggressive treatment. Established guidelines for post-therapy monitoring in BLBC feature mammography and clinical examination which frequently fail to identify local tumor relapse at a sufficiently early stage.

Magnetic resonance imaging (MRI) and FDG-PET/CT offer a comparably higher sensitivity and
specificity for detection and characterization of BC relapse . However, differentiation of recurrent BC from inflammatory or infectious processes, and the identification of small lesions (tumor size <20 mm) still impose challenges for FDG-PET. [18-F]c-Met targeted imaging could provide such a tool to further improve the performance of post-treatment surveillance, and could aid patient stratification for targeted therapy. In this pilot study we shall use 12 mice for evaluation [18F] c-MET for detection of early stage loco regional recurrence breast cancer.