Tumor models and specific contrast agents for small animal imaging in oncology

Abstract

a b s t r a c tDespite the widespread use of various imaging modalities in clinical and experimental oncology without or with combined application of commercially available nonspecific contrast agents (CAs), development of tissue-or organ-or disease-specific CAs has been a continuing effort for pursuing ever-improved sensitivity, specificity, and applicability. This is particularly true with magnetic resonance imaging (MRI) due to its intrinsic superb spatial/temporal/contrast resolutions and adequate detectability for tiny amount of substances. In this context, research using small animal tumor models has played an indispensible role in preclinical exploration of tissue specific CAs. Emphasizing more on methodological and practical aspects, this article aims to share our cumulated experiences on how to create tumor models for evaluation and development of new tissue specific MRI CAs and how to apply such models in imaging-based research studies. With the results that are repeatedly confirmed by later clinical applications in cancer patients, some of our early preclinical studies have contributed to the designs of subsequent clinical trials on the new CAs, some studies have predicted new utilities of these CAs; and other studies have led to the discoveries of new tissue-or disease-specific CAs with novel diagnostic or even therapeutic potentials. Among commonly adopted tumor models, the chemically induced and surgically implanted nodules in the liver prove very useful to simulate primary and metastatic intrahepatic tumors, respectively in clinical patients. The methods to create tumor models have eased procedures and yielded high success rates. The specific properties of the new CAs could be outshined by intraindividual comparison to the commercial CAs as nonspecific controls. Meticulous imaging-microangiography-histology matching techniques guaranteed colocalization of the lesion on in vivo MRI and postmortem tissue specimen, hence correct imaging interpretation and longstanding conclusions. As exemplified in the real study cases, the present experimental set-up proves applicable in small animals for imaging-based oncological investigations, and may provide a platform for the currently booming molecular imaging in a multimodality environment.

Pharmacokinetics of gelatin sponge microparticles in a rabbit VX2 liver tumor model of hepatic arterial chemoembolization

“…The rabbit model of VX2 liver metastasis was established by referring to the method of Ni et al [15]. Hepatic implantation of the VX2 carcinoma was accomplished under general i.v.…”

Multiparametric MRI biomarkers for measuring vascular disrupting effect on cancer

“…Thus, response to the same treatment may differ depending on tumor location and host-tumor interaction, because the organ-specific regulation of the balance between pro-and anti-angiogenic factors is responsible for the different angiogenesis activities [2,4,62,72] . As a result, tumor models of orthotopic transplantation into visceral organs of host animals with intact immune functions are thought to be more relevant to the conditions of clinical patients in terms of better mimicking tumor microenvironment, therefore, the treatment outcomes are more translatable into patients [62,72] . For imaging studies of VDA effects in small rodents, image quality has been shown to be satisfactory, even for organs susceptible to motion artifacts with nonrespiratory-gated acquisition at a clinical magnet [56] .…”

Proper definitions of MRI contrast enhancement in liver tumors

“…1D of the article by Narita et al [1] is to date the closest clinical finding comparable to what has been reported in rats [3,4,9]. In contrast, other experimental studies have failed to convincingly demonstrate the true positive TCE in rodent hepatic tumor models [10,11].…”

“…1D of Narita et al [1] and in animal results [3,4,9]. The most straightforward approach is to calculate the postcontrast tumor-to-liver contrast ratio (CR), i.e., CR = SI tumor /SI liver .…”