Small-animal positon emission tomography (SA-PET) imaging is a powerful tool in performing preclinical studies in tumor-bearing rodents and is being increasingly used to evaluate metabolic response to treatment, particularly within the framework of new drug development [1, 2]. Animal models include abdominal tumors that arise in transgenic animals or tumors that arise after engraftment of exogenous malignant cells.
In abdominal tumor models, a moderate-to-high physiological uptake in the gut is observed with many tracers, including 18F]fluorodeoxyglucose (18F-FDG) and 18F]fluorothymidine (18F-FLT), which may hamper tumor detection. Moreover, anatomical landmarks are lacking on PET images alone. In this setting, correlative computed tomography (CT) acquisition is useful to improve the localization of tracer uptake and provides faster and more accurate attenuation correction than attenuation correction obtained with external gamma sources . However, an unenhanced CT scan does not allow delineation of tumors from the surrounding organs as both have similar CT attenuation characteristics [4, 5]. This drawback is particularly an issue in nude mice and nude rats, which lack abdominal fat. The use of iodinated contrast agents solves this problem. Iodinated agents that are typically used in the clinical setting cannot be used for intravenous injections in rodents because microCT devices are not fast enough to image animals before the contrast media is cleared from the blood. Therefore, dedicated iodinated contrast agents have been developed for preclinical research. Two long-lasting intravascular contrast media agents, eXIA 160XL (Binitio Biomedical, Inc., Ottawa, Canada) and Fenestra VC (Advanced Research Technologies Inc., Saint-Laurent, Quebec, Canada) [6–9], are commercially available. eXIA 160XL is a single-phase contrast agent that provides peak contrast enhancement in the spleen, liver, and vessels within the first hour after injection, while Fenestra VC is a dual-phase contrast agent that provides blood-pool enhancement for more than 2 h after intravenous injection followed by liver enhancement. Also available is Fenestra LC (Advanced Research Technologies Inc.), a contrast agent offering liver and spleen enhancement for durations reported to be as long as 7 days in mice. In addition, the clinically used iodinated agents can be injected by the intraperitoneal route to improve delineation of abdominal tumors .
To our knowledge, studies comparing the diagnostic performance of unenhanced SA-PET/CT versus contrast-enhanced SA-PET/CT with protocols including one or more of the contrast agents described above are lacking. Moreover, clinical PET/CT studies have shown that contrast agents may result in overestimation of standardized uptake values on images corrected for attenuation with attenuation maps derived from CT [11–15].
The aim of this study was to perform a comprehensive evaluation of the diagnostic performance and the accuracy of SA-PET quantitative values in contrast-enhanced versus unenhanced SA-PET/CT by phantom and animal studies in abdominal tumor-bearing rats and mice. For that purpose, we used the NEMA NU 4–2008 image quality phantom, which provides a standardized assessment of the overall image quality and accuracy of attenuation and scatter corrections ; we also used homemade phantoms mimicking tumors surrounded by contrast media. In addition, we scanned a large cohort of animals with various contrast media protocols to evaluate both the diagnostic and quantitative accuracies of contrast-enhanced SA-PET/CT (CEPET/CT) versus unenhanced SA-PET/CT (UEPET/CT).