RE:RE:RE:RE:RE:RE:RE:TH2101Sorry to come again with that, but in the new corporate presentation one item in the section "SORT1+ TechnologyTM: Future Opportunities" is this:
Gain better understanding of the exact MOA, impact on surrounding tissue/tumor microenvironment (TME) and fate of conjugate once it enters the cell and is degraded One thing the imaging TH19P01-DOTA-Ga68 would allow to do, is to follow over time the fate of this peptide-linker-isotope conjugate in the human body which is very likely to be similar to those of othe TH19P012 based PDCs. After injection they just need to do multiple scans to follow the distribution of the peptide-linker-isotope in the human body and tumors. It would also help a lot to determine the optimal dosing and understand the dynamic of receptor saturation or occupancy versus the dose given.
One thing that was not discussed here yet, is the fact that if you give a really high dose of a TH19P01 based PDC like TH1902, at some point it will saturate the available sortilin recptors everywhere in the body. There is a limited number of these receptors, and when they undergo internalization (endocytosis), they are no longer on the membrane and they are not instantly replaced. So at a very high dose, it is likely that the TH19P01 based PDC will be unable to enter cancer cells, or any other cell expressing sortilin, because all the sortilin receptors will have been occupied or internalized, so the excess PDC will remain in the bloodstream where it will be degraded over time, resulting in more toxicity from free docetaxel or other cytotoxic drug.
Remeber the reference Wino gave us about a monoclonal antibody aiming at sortilin for brain disorder. The idea was to occupy the sortilin receptors to make them unavailable to internalize its natural ligand progranulin. It means that there is a real possible saturation effect of the sortilin receptors. Again, imaging with TH19P01-DOTA-Ga68 would be an excellent tool to understand that process versus dose level, and also versus the level of sortilin expression in a given patient. Because the level of sortilin expression, or what we could call the sortilin load in a patient will be very important to determine the ideal dose for treatment. For sure, at this early stage, it is not necessary to have such a fine tuned approach, but in the future, to be able to get the full potential of the SORT1+ platform, an non invasive imaging tool would be such a great way to optimize the whole treatment.
jfm1330 wrote: Hey Thera people! If somebody out there is reading this board, show this to Christian Marsolais. I cannot believe he does not already know about this possibility, but it would be such a fantastic complimentary tool to the SORT1 plaform. I cannot understand why they are not puting it forward as a possibility. I know it looks like an obssession of mine, but it seems a great possibility that is so obvious.