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In Vitro and In Vivo Characteristics of [Iodine-125] 3-(R)-Quinuclidinyl (S)-4-Iodobenzilate

Radiopharmaceutical Chemistry, George Washington University Medical Center, Washington, DC

Correspondence: For reprints contact: Raymond E. Gibson, MD, Research Imaging, Merck, Sharp and Dohme Research Laboratories, WP-44C, West Point, PA 19486.

ABSTRACT

The radioiodinated muscarinic acetylcholine receptor antagonist, [¹²⁵I] 3-quinuclidinyl 4-iodobenzilate, has two high affinity diastereomeric forms, the (R,R) and (R,S)-isomers. The (R,S)-diastereomer is only threefold lower in affinity than the (R,R)-isomer, but the kinetic properties are considerably different—the dissociation rate constant is 13-fold faster for the (R,S)-isomer and the association rate constant is two to threefold faster. The calculated affinity is therefore only fourfold lower. In vivo, the clearance of (R,S)-4IQNB from receptor rich tissue is also more rapid than that of the (R,R)-isomer, that is a reflection of the more rapid in vitro kinetic properties since the physicochemical properties and the metabolic clearance of the diastereomers is the same.

FOOTNOTES

^* Present address: The Squibb Institute for Medical Research, New Brunswick, NJ.