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The Journal of Nuclear Medicine Vol. 20 No. 8 865-870
© 1979 by Society of Nuclear Medicine
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The Distribution of the Muscarinic Acetylcholine Receptor Antagonists, Quinuclidinyl Benzilate and Quinuclidinyl Benzilate Methiodide (both tritiated), in Rat, Guinea Pig, and Rabbit

Raymond E. Gibson, William C. Eckelman, Frank Vieras and Richard C. Reba

School of Medicine, George Washington University Medical Center, Washington, D.C.
Armed Forces Radiobiology Research Institute, Bethesda, Maryland

Correspondence: For reprints contact: Raymond E. Gibson, George Washington University Medical Center, School of Medicine, 2300 Eye St., N.W., Washington, D.C. 20037

ABSTRACT

The distribution of [3H]quinuclidinyl benzilate and its methiodide salt was determined in rat, guinea pig, and rabbit. Accumulation in the myocardium of up to 2% of the injected dose per gram of tissue was obtained with both compounds, providing heart-to-blood ratios of ~30 and heart-to-lung ratios of ~4. The accumulation in the heart was blocked (89%) by preinjection of atropine. The distribution of tritium in rabbit heart corresponds to the muscarinic receptor densities determined in vitro. Calculation of the theoretical maximum for the bound-to-free ratio, based on in-vitro equilibrium binding isotherms, resulted in ratios in reasonable agreement with the experimental results. Because of the high accumulation in the heart with low serum concentration, we conclude that the methiodide salt of quinuclidinyl benzilate represents an ideal parent structure for the design of a receptor-binding gamma-emitting radiopharmaceutical for imaging of the myocardium.






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Copyright © 1979 by the Society of Nuclear Medicine.