Contrast‐enhanced MRI of murine sponge model for progressive angiogenesis assessed with gadoteridol (ProHance) and gadocoletic acid trisodium salt (B22956/1)

Abstract

Purpose:To investigate the potential value of MRI for noninvasive assessment of angiogenesis in a murine model exploiting the properties of two contrast agents, gadoteridol (ProHance) and gadocoletic acid trisodium salt (B22956/ 1). Materials and Methods:Biocompatible sponges were implanted in both mice flanks. Stimulated sponges contained human recombinant basic fibroblast growth factor (bFGF) as the angiogenic agent; control sponges contained vehicle. Angiogenesis was evaluated by MRI after injection of extravascular (ProHance) or blood-pool (B22956/1) contrast agents at different times after sponge implantation. Sponges signal intensity enhancement was calculated both as the relative enhancement and the rate of relative enhancement. Results from MRI were validated by classic biochemical (hemoglobin level and protein content) and morphological (histology) assays. Results:The intrinsic different properties of ProHance and B22956/1 in wash-in and wash-out kinetics were useful to detect progressive vascularization and the establishment of a functional vascular network in the implants. Moreover, MRI allowed the appreciation of differences in neovessel colonization between bFGF-treated sponges and controls. Hemoglobin level, protein content, and histology confirmed the sponge vascularization and MRI results. Conclusion:Contrast-enhanced MRI is a reliable tool to study vascular characteristics in animal models of angiogenesis. The different kinetic properties of contrast agents can provide evidence of different functional neovascularization aspects and levels.

Onset and Maintenance of Angiogenesis in Biomaterials:In VivoAssessment by Dynamic Contrast-Enhanced MRI

“…19 Ramponi et al used contrast-enhanced MRI to show that fibroblast growth factor improves angiogenesis in collagen sponges, placed subcutaneously in mice. 20 They compared relative values of enhanced uptake of two different contrast agents. DCE-MRI is utilized in oncologic studies to evaluate the success of anti-angiogenic therapy over time.…”

Chemistry of MRI Contrast Agents: Current Challenges and New Frontiers

“…A number of additional albumin targeting functionalities also have been appended to relaxation agents for intravascular imaging. For example, the Gd-DTPA based agents B22956/1, which have been extensively evaluated as an angiographic contrast agent, utilizes 3-deoxycholic acid as an albumin targeting group. − ,− A biological function of serum albumin is to transport lipopilic anions. The high concentration of serum albumin and its ability to promiscuously bind many classes of compounds makes it possible to generate a large number of albumin-targeted agents. − Additional examples of albumin binding MRI contrast agents have been reported, ,,− but there are too many to acknowledge even for this extensive review.…”

Ultrahigh‐field DCE‐MRI of angiogenesis in a novel angiogenesis mouse model

“…The model that came closest to these criteria was the subcutaneous sponge implant model introduced by Andrade et al in 1987 (25). This model provides a scaffold for dividing and migrating endothelial cells, and the size and shape of the implanted scaffolds are consistent throughout the experiment (26)(27)(28). The angiogenesis process is propelled by a mild foreignbody response making use of the animals own growth factors, and the neovasculature is created within the scaffold making it easily identifiable.…”