Regional intracellular pH shift: a proposed new mechanism for radiopharmaceutical uptake in brain and other tissues.
This paper proposes a new mechanism for radiopharmaceutical uptake, which may be applicable to a variety of clinical studies. Many tissues and organs have low intracellular pH, either normally or as a result of various metabolic disturbances. We have developed a series of compounds that are neutral and lipid-soluble at blood pH. These molecules can diffuse freely into cells. In those regions where intracellular pH is low, they pick up a hydrogen ion and become charged. In this form they are no longer lipid-soluble and are trapped because they cannot diffuse out of the cell. Studies of the brain uptake of two compounds of this type, Se-75 labeled di-beta-(morpholinoethyl)-selenide (MOSE) and di-beta-(piperidinoethyl)-selenide (PIPSE), demonstrate the application of the principle.
D000818:Animals; D001812:Blood-Brain Barrier; D001826:Body Fluids; D001921:Brain / Q000000981:diagnostic imaging*; D002463:Cell Membrane Permeability; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid; D008297:Male; D011868:Radioisotopes; D011877:Radionuclide Imaging; D051381:Rats; D012643:Selenium / Q000378:metabolism; D012995:Solubility; D014018:Tissue Distribution
D011868:Radioisotopes; D012643:Selenium