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Synthesis and biological evaluation of iodine‐125 iodocaramiphen. A potential M 1 muscarinic imaging agent for SPECT
Author(s) -
McPherson Daniel W.,
Knapp F. F. Russ,
Hudkins Robert L.
Publication year - 1994
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580340306
Subject(s) - muscarinic acetylcholine receptor , chemistry , biodistribution , iodine 123 , muscarinic antagonist , in vivo , antagonist , muscarinic acetylcholine receptor m1 , receptor , iodine , specific activity , selectivity , pharmacology , in vitro , endocrinology , medicine , biochemistry , organic chemistry , enzyme , biology , microbiology and biotechnology , catalysis
Iodocaramiphen ( 2 ) is a selective muscarinic antagonist which binds in vitro with high affinity and selectivity to the M 1 subtype of the muscarinic receptor. We report the synthesis of iodine‐125 labeled iodocaramiphen ([ 125 I]‐ 2 ) via a tributylstannyl intermediate ( 3 ) in 50% radiochemical yield with a specific activity greater than 1000 mCi/μmol. Biodistribution studies in female Fischer rats demonstrated that [ 125 I]‐ 2 had significant cerebral localization (0.7% injected dose/gram) at 60 minutes post injection. The uptake of activity washed out rapidly from the brain, however, and did not demonstrate specific uptake in those cerebral regions rich in muscarinic receptors. In addition, preinjection with (±)‐QNB (5 mg/kg) blocked uptake of approximately 25% of the injected radiolabel in the brain at 2 hours. The non‐selectivity of 2 toward muscarinic receptors in vivo may result from the metabolism of 2 by various esterases or the affinity of 2 for sigma sites in the brain.