Performance of an Intravascular Tantalum Oxide-Based Nanoparticle Computed Tomography Contrast Agent in Preclinical Hepatic Tumor Detection.

Abstract

Background: Noniodinated intravenous contrast agents have shown significant potential to improve computed tomography (CT) imaging; however, in vivo evidence for impact on lesion detection remains scarce.

Purpose: The aim of the study was to compare a novel intravenous carboxybetaine zwitterionic-coated tantalum oxide (TaCZ) nanoparticle contrast agent to clinical iodinated contrast agent for the detection of liver tumors in a rabbit tumor model at CT.

Methods: Following hepatic implantation of VX2 tumors, n = 10 rabbits were repeatedly scanned on a clinical CT system before and at 40, 105, and 180 seconds after intravenous contrast injection of 540 mg element (Ta or I) per kilogram of body weight using TaCZ or iopamidol. After contrast elimination, imaging was repeated with the other contrast agent in each rabbit. Findings were compared to gross pathology. Three readers independently reviewed n = 114 randomized image series for hepatic tumors and rated conspicuity on a 5-point scale (1 = barely visible to 4 = obvious; 0 = not detected). Regions of interest drawn by readers were used to calculate contrast to noise ratio. Metrics were compared between contrast agents for different tumor size categories (3-6 mm, >6-11 mm, >11-14 mm, >14 mm) and for venous scan delays between contrast agents.

Results: TaCZ provided higher hepatic contrast enhancement resulting in superior Contrast-to-noise ratio (CNR) of hepatic tumors at all examined venous contrast delays (5.7-6.9 vs 3.9-4.5; all P < 0.001) compared to iopamidol. This translated into improved overall sensitivity (all P < 0.001) and detection of small hepatic tumors ≤11 mm (all P≤0.002). In addition, compared to iopamidol, TaCZ showed higher tumor conspicuity in all subgroups. Larger lesion size and early contrast delay were associated with improved lesion detection for both contrast agents.

Conclusions: Experimental TaCZ nanoparticles showed higher hepatic contrast enhancement and improved the detection and conspicuity of hepatic tumors at all sizes and scan delays compared to iopamidol, with sustained intense contrast enhancement in delayed venous phase up to at least 180 seconds.