We recently discovered that our Fenestra HDVC contrast agent for microCT imaging could be administered via injection into the intraperitoneal (IP) space.
Following IP injection, Fenestra HDVC enters into the blood stream and then the liver.
Does anyone know what the mechanism of uptake into blood is following IP injection?
We noticed the lymph nodes had a strong signal on the microCT scan 24 hours after injection (see attached) and so we presume they are playing a role.
Here is some more info on Fenestra HDVC from Nature Sci. Reports article. ref. https://medilumine.com/new-publication-on-fenestra-hdvc-in-nature-reports
Hi Stephen,
Hope you are well. There is some work that has shown that IP injections are captured by lymphatic / macrophage uptake. One random reference, but there are newer papers:
https://www.sciencedirect.com/science/article/abs/pii/S0022354915468649
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Hi Dr. Lee,
Nice to hear from you here and I hope you are well. Thank-you for sharing the reference suggesting lymphatic drainage as major elimination pathway from intraperitoneal space. It's interesting to see in this study that the liposomes are retained in lymph and lymph nodes. We see minimal amounts of such retention with Fenestra HDVC which may indicate that lymphatic drainage is enabling the absorption of Fenestra HDVC lipid spheres in blood but that our smaller sized lipid particles are not being retained in lymph and lymph nodes. Some other elimination routes for us to explore could be the blood vessel network in peritoneal cavity, mesenteric veins, and absorption through stomata in the diaphragm muscle.
Hi Dr. Marchant, The vascular network in the omentum is the usual pathway for agent uptake. This is what we find when using smaller molecular weight IP injections. This serves as a poor-mans IP technique in some cases where our techs don't have good animal skills or as a longer-time infusion technique. The MW of your Fenestra is pretty big so I wouldn't think that direct infusion of the particle is part of the mechanism. The suggestion of macrophage transport is interesting but that should just take everything to the liver. It's been a number of years since I've played with Fenestra and I don't recall the hold time for the particle in vivo. I do recall that the particle has a lifetime over which the PEG is degraded and the lipid core then starts leaking payload. Could it be releasing some of the low MW MRI contrast into the peritoneum which then gets picked up by the circulation? Interesting find. Hope you publish it when you've worked it out.
Nice to hear from you Dr. Morris!
The Fenestra HDVC formulation is now based in a new and improved oil in water emulsion that circulates in blood for longer periods compared to the previous Fenestra VC formulation. Information on contrast kinetics was recently published in Nature Sci. Reports and you can get more info here. ref. https://medilumine.com/new-publication-on-fenestra-hdvc-in-nature-reports.
We are still working on the exact time course for contrast enhancement following IP injections.
It seems like the lymph nodes are playing an important role for uptake of Fenestra HDVC into blood. Compared to IV injections, there seems to be much more contrast in the lymph nodes with IP administration. See attached image of lymph nodes 17 hours after IP injection. H. Douglas Morris Yueh Z Lee Felix Gremse
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