Our hepatocyte selective Fenestra LC contrast agent contains nano sized lipid spheres which pick up APO-E in blood and target hepatocytes of liver. The lipids of the Fenestra LC polyiodinated triglyceride emulsion are metabolized by hepatocytes and eventually eliminated in bile.
We have observed that Fenestra LC undergoes significant uptake in placental tissues in pregnant mice and rats. This occurs after the agent has cleared from the vasculature.
What cell type of mice placenta could be responsible for such an uptake?
Thank-you!
Stephen Marchant
Here is the picture showing the liver contrast and placental contrast with Fenestra contrast
Hi Stephan,
I have no direct experience, and am relying on rather old discussions with colleagues in that field years ago.
There is a form of macrophage (I believe unique to placenta) that are closely associated with the forming vascular. I would not be surprised if that would be the cell type. This assumes that the tissues of the mouse/rat are similar enough to the sheep/human for those discussions to be relevant.
Good Luck.
Hi Stephen and Bill, This is an interesting find. Fenestra has a number of interactions with mice physiology that we have found to be strain dependent. This is the first report I've heard of a placental uptake and like Bill has postulated targeted Macs could be transporting it. We have seen some evidence of that with liver transport in certain reactive species. C57Blk/6 has especially reactive transport of VC and LC in certain cross strains to overloading the liver. Did the dam deliver healthy pups post imaging or was this a terminal exam? If terminal did histology show any locus for the LC in the placenta? Thanks, Doug
Douglas,
Thank-you for sharing. Unfortunately, this was a terminal exam and no histology was performed on performed to show the locus of Fenestra LC.
It would seem that RES uptake of Fenestra can be activated when the hepatocyte uptake is saturated. The only publication I know of that briefly mentions this topic was from UCLA. Ref. http://jnm.snmjournals.org/content/48/supplement_2/346P.4.short
Fenestra has had a quite a fascinating history of acquisitions from Molecular Biosystems, to MetaProbe, to Alerion, to ART Advanced Research Technologies and finally to MediLumine where it has been successfully made and commercialized since 2014. It should be noted that many excipients used in formulation of Fenestra such as triolein, soy PC, cholesterol, alpha tocopherol (vitamin E) are commercially available from different suppliers with different purity levels and it is not clear how raw material sourcing could have been related to the strain dependant uptake that you had observed.
The newest version of Fenestra will be called Fenestra LDHD (Low Dose High Definition) and will have a higher iodine concentration with only a few excipients. The hepatocyte selective feature will be retained which is important for functional imaging in staging and monitoring liver diseases. Ref. https://www.medilumine.com/wp-content/uploads/2020/01/Micro-CT-Contrast-Agents-for-Detection-of-Murine-Non-Alcoholic-Fatty-Liver-Disease.pdf. In addition, the Fenestra LDHD will allow for vascular imaging. It would be interesting to repeat your study with different mouse strains to see if you still get the variable uptake with the new version of Fenestra which will only have a few excipients.
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