Standard imaging cannot reliably predict the nature of renal tumors. Among malignant renal tumors, clear cell renal cell carcinoma (ccRCC) is the most common histological subtype, in which the vascular endothelial growth factor 2 (VEGFR-2) is highly expressed in the vascular endothelium. BR55, a contrast agent for ultrasound imaging, consists of gas-core lipid microbubbles that specifically target and bind to the extracellular portion of the VEGFR-2. The specific information provided by ultrasound molecular imaging (USMI) using BR55 was compared with the vascular tumor expression of the VEGFR-2 by immunohistochemical (IHC) staining in a preclinical model of ccRCC. Patients' ccRCCs were orthotopically grafted onto Nod-Scid-Gamma (NSG) mice to generate patient-derived xenografts (PdX). Mice were divided into four groups to receive either vehicle or axitinib an amount of 2, 7.5 or 15 mg/kg twice daily. Perfusion parameters and the BR55 ultrasound contrast signal on PdX renal tumors were analyzed at D0, D1, D3, D7 and D11, and compared with IHC staining for the VEGFR-2 and CD34. Significant Pearson correlation coefficients were observed between the area under the curve (AUC) and the CD34 (0.84, p < 10-4), and between the VEGFR-2-specific signal obtained by USMI and IHC (0.72, p < 10-4). USMI with BR55 could provide instant, quantitative information on tumor VEGFR-2 expression to characterize renal masses non-invasively.
International journal of molecular sciences. 2023 Nov 11*** epublish ***
Jean Courcier, Ingrid Leguerney, Baya Benatsou, Sibylle Pochon, Isabelle Tardy, Laurence Albiges, Paul-Henry Cournède, Alexandre De La Taille, Nathalie Lassau, Alexandre Ingels
Department of Urology, Henri Mondor Hospital, University of Paris Est Créteil (UPEC), 94000 Créteil, France., Biomaps, UMR1281, INSERM, Centre National de la Recherche Scientifique (CNRS), Commissariat à l'Energie Atomique (CEA), Université Paris Saclay, 94800 Villejuif, France., Bracco Suisse SA, 1201 Geneva, Switzerland., Department of Urological Oncology, Gustave Roussy Cancer Campus, 94805 Villejuif, France., Laboratory of Mathematics and Computer Science (MICS), CentraleSupélec, Université Paris-Saclay, 91190 Gif-Sur-Yvette, France.