Interstitial MR Lymphography in Mice: Comparative Study with Gadofluorine 8, Gadofluorine M, and Gadofluorine P

Abstract

Purpose: We investigated the characteristics and capability of interstitial MR lymphography in mice using gado‰uorine 8, gado‰uorine M, and gado‰uorine P.Methods: We injected healthy mice with 0.5 mmol of Gd gado‰uorine 8, gado‰uorine M, or gado‰uorine P subcutaneously into the right rear footpad and assessed the time courses of contrast enhancement in the lymph nodes. Six mice were studied for each contrast agent. We also used gado‰uorine M to assess the lymphatic pathway from the right and left rear feet or tail.Results: Contrast enhancement was demonstrated for the right popliteal, sacral, and iliac lymph nodes in all mice 5 minutes after injection of each of the 3 agents and decreased gradually. Enhancement in the lymph nodes was still detectable 30 minutes after injection of gado‰uorine 8 or gado‰uorine M. Enhancement became obscure sooner after gado‰uo-rine P injection and was mildly stronger with the other 2 contrast agents. Clear diŠerences were found in the hepatobiliary and urinary kinetics of the 3 agents. Gado‰uorine M injected into various sites delineated the lymphatic pathway from the site of injection.Conclusion: Interstitial MR lymphography using gado‰uorine 8, gado‰uorine M, and gado‰uorine P oŠered clear visualization of the lymphatic pathway in healthy mice during a su‹cient imaging time window, and allowed repeated assessment of the pathway and clariˆcation of the lymphatic system.

PEG‐poly(L‐lysine)‐based polymeric micelle MRI contrast agent: Feasibility study of a Gd‐micelle contrast agent for MR lymphography

“…Micelle‐forming agents, such as gadofluorine 8 and gadofluorine P, are also used for MRL. They demonstrated a rather long retention to lymph node, lasting 60–90 minutes …”

Emerging lymphatic imaging technologies for mouse and man

“…Indirect MR lymphangiography in the legs of lymphedema patients (11)(12)(13) has excellent resolution and better visualization than lymphoscintigraphy (14) (Figure 2, A and B), but this technique has not been used for non-invasive imaging of truncal lymphatics, as has been demonstrated with x-ray direct lymphan-giography. With advances in MR contrast agent development, indirect MR lymphangiography has enabled the localization of LNs and peripheral lymph drainage pathways in animals (15)(16)(17)(18). Albumin-binding gadolinium-based agent gadofosevet, recently FDA-approved for use in hemovascular applications, might also potentially be employed off-label for interstitial, indirect MR lymphangiography (14).…”

Magnetic resonance imaging of the pancreas in streptozotocin-induced diabetic rats: Gadofluorine P and Gd-DOTA

“…The 6 diabetic rats and the 5 controls underwent MRI for 3 d. We performed MRI first with Gd-DOTA and 24 h later with Gadofluorine P because the elimination half-life of Gd-DOTA is much shorter than that of Gadofluorine P [19,25] . The imaging time point for Gd-DOTA and Gadofluorine P was based on our time-intensity curve data ( Figure 3) and data from other studies [13,23] . The rats were scanned in the supine position with no respiratory gating.…”

“…Gadofluorine agents are amphiphilic gadolinium complexes, synthesized by adding a perfluoroctyl chain to a gadoliniumcontaining macrocycle (Figure 2) [13] ; therefore, they form micelles in water. In blood or extracellular tissue, Gadofluorine agents strongly interact with hydrophobic proteins (e.g., albumin, extracellular matrix proteins), leading to a breakdown of the micelles [17,18] .…”

“…We used Gadofluorine P (invivoContrast GmbH, Berlin, Germany)-enhanced magnetic resonance imaging (MRI) in a rat model of STZ-induced diabetes. Gadofluorine P is a gadolinium (Gd)-based T1 contrast agent; it is commercially available but not approved for clinical use [13] . We hypothesized that increased vascular permeability of the islets could be detected using longcirculating Gadofluorine P, which extravasates from leaky vessels into the surrounding tissue and binds to extracellular proteins.…”