Prospective pilot study with [⁸⁹Zr]Zr-girentuximab PET/CT: CA-IX imaging in metastatic triple negative breast cancer (OPALESCENCE).

Abstract

Metastatic triple negative breast cancer (mTNBC) is aggressive with drug-resistance. Evaluating new markers is an unmet need. Anhydrase carbonic-IX (CA-IX), a hypoxia-mediated breast tumor growth regulator, is important for maintaining BC stem cells within a hypoxic region. This pilot prospective study "OPALESCENCE" assessed [⁸⁹Zr]Zr-DFO-89Zr-girentuximab (TLX250-CDx) positron emission tomography/computed tomography (PET/CT), in comparison with [¹⁸F]F-fluoro-deoxy-glucose (FDG) PET/CT in mTNBC patients (NCT04758780). Patients underwent FDG and TLX250-CDx PET/CT and conventional imaging (CI) if needed. Intravenous administration of 37±10% MBq TLX250-CDx was performed, The PET/CT was acquired at Day 3 or 5 post injection. Gold standard composite was based on FDG PET/CT, CI and follow-up. Tumor standard uptake values (SUV_max and SUV_mean) were measured, and tumor burden analyzed using total tumor volume (TTV). Immunohistochemistry (IHC) was performed with a Bond RX (Leica) fully automated research stainer with CA-IX antibody (clone EP161). Twelve mTNBC patients were included. Of 273 lesions confirmed with the gold standard, 231 were detected by TLX250-CDx and 264 by FDG PET/CT. Overall sensitivity of TLX250-CDx PET/CT was 87.5% with 100% sensitivity for breast, skin, and adrenal gland, and 88.0% and 91.9% for node and bone lesions respectively. In contrast to FDG PET/CT, TLX250-CDx PET/CT revealed brain metastases. Tumor burden evaluated with TTV was equivalent between both PET/CT methods. For 7/12 patients, IHC analyses showed CA-IX expression lesions from 100% to 10% with an intensity from 3+ to 2+. No safety issue was reported after TLX250-CDx injection. [⁸⁹Zr]Zr-girentuximab PET/CT is a sensitive imaging method and offers promise for novel theranostics for mTNBC patients. Clinical trial.gov, the unique identifying number: NCT04758780, date of registration: 16/02/2021.