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Carbon-11-Forskolin: A Ligand for Visualization of the Adenylate Cyclase-Related Second Messenger System

Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo
Faculty of Hygienic Sciences, Kitasato University, Sagamihara, Kanagawa, Japan

Correspondence: For correspondence or reprints contact: Dr. Toru Sasaki, Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi, Tokyo, 173, Japan.

ABSTRACT

To visualize the adenylate cyclase (AC)-related second messenger system, [¹¹C]forskolin, [¹¹C]1-acetyl-7-deacetytlforskolin, [¹¹C]1,9-dideoxyforskolin and [¹¹C]1-deoxyforskolin were synthesized by acetylation of the respective deacetyl-precursors using [¹¹C]acetylchloride and dimethylaminopyridine. The radio-chemical yield of [¹¹C]forskolin, [¹¹C]1-acetyl-7-deacetylforskolin, [¹¹C]1,9-dideoxyforskolin and [¹¹C]1-deoxyforskolin calculated from trapped [¹¹C]C0₂ were 5%, 10%, 15% and 18%, respectively. Since the 1- and 9-OH groups on the forskolin structure are critical for specific binding to AC (active type), we considered [¹¹C]1-acetyl-7-deacetytforskolin, [¹¹C]1,9-dideoxyforskolin and [¹¹C]1-deoxyforskolin to be nonspecific forskolin analogs. A comparative study of [¹¹C]forskolin and its analogs on then-octanol/phosphate buffer (pH 7.4) partition ratio showed that [¹¹C]1-acetyl-7-deacetylforskolin has similar physical properties to [¹¹C]forskolin. In the mouse heart, kidneys, liver and lungs, more [¹¹C]forskolin accumulated than [¹¹C]1-acetyl-7-deacetylforskolin. Moreover, simultaneous [¹¹C]forskolin with forskolin (10 µg) administration reduced the accumulation of [¹¹C]forskolin particularly in the heart to the level of [¹¹C]1-acetyl-7-deacetylforskolin. These results indicate that [¹¹C]forskolin would be a useful imaging agent for the AC-related second messenger system.