123I-SCH 23982 is not suitable for dopamine D1 receptor imaging in vivo in the human brain

Design of Radioiodinated Pharmaceuticals: Structural Features Affecting Metabolic Stability towards in Vivo Deiodination

“…In fact, there is good evidence of enzymatic in vivo deiodination occurring specifically on iodotyramine derivatives [i.e., derivatives of 4‐(2‐aminoethyl)‐2‐iodophenol ( 25 ), Figure ]. The process is very likely enzyme‐catalyzed because of its intrinsic specificity: radiolabeled MIT and compounds 25 , 26 , and 27 are quickly deiodinated (MIT more rapidly than 27 ), whereas even 28 (exogenous radioactive enantiomer of MIT) is instead metabolically stable . Minimal variations in the structure of MIT, such as α‐ or O ‐methylation (compounds 29 or 30 , respectively) also result in almost complete retention of the radionuclide .…”

“…This behavior can be explained in terms of the selectivity of the deiodinase enzyme: compound 31 , being a complex natural product, has a strained three‐dimensional structure that likely does not fit the catalytic cleft of the deiodinating enzyme. On the other hand, compound 27 is metabolically not stable . Its tyramine moiety is embedded in a structure less strained than that in 31 , allowing the compound to adjust its three‐dimensional structure to fit the catalytic cleft of the deiodinating enzyme.…”