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Regional Intracellular pH Shift: A Proposed New Mechanism for Radiopharmaceutical Uptake in Brain and Other Tissues

State University of New York at Buffalo, Buffalo, New York

Correspondence: For reprints contact: Hank F. Kung, Dept. of Nuclear Medicine, VA Medical Center, 3495 Bailey Ave., Buffalo, NY 14215.

ABSTRACT

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-ß-(morpholinoethyl)-selenide (MOSE) and di-ß-(piperidinoethyl)-selenide (PIPSE), demonstrate the application of the principle.

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