Quantification of aromatase binding in the female human brain using [¹¹C]cetrozole positron emission tomography

Abstract

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A comparative study on Suzuki‐type 11C‐methylation of aromatic organoboranes performed in two reaction media

“…Prior this study we have produced [ 11 C]Cetrozole for clinical imaging studies and [ 11 C]UCB-J for preclinical imaging studies using published synthesis protocols. 5,19 As already shown, we could increase the RCY of [ 11 C] UCB-J when trifluoroborate precursor by changing the reaction medium from DMF/water to THF/water. Here, we demonstrate that THF/water can also increase the RCY of [ 11 C]cetrozole synthesized from pinacol ester precursor.…”

“…In 11 C-methylations, pinacol esters have shown to react in mixtures where no water is added as is seen for example in the synthesis of [ 11 C] cetrozole, suggesting that pinacol esters may react directly with oxo-palladium complexes or exhibit favorable hydrolysis rate at semi-dry conditions to form suitable concentrations of boronic acid in situ. 8,13,15,19,[27][28][29] This may explain why the RCY of 1-[ 11 C]methylnaphthalene was similar for the pinacol ester and the boronic acid (Table 1). Being stable in anhydrous conditions, the MIDA ester needs to hydrolyze to boronic acid before the Suzuki type coupling reaction can be performed.…”

“…In the synthesis of [ 11 C]cetrozole in DMF, all reagents were weighed in the same vessel, DMF was added, and reaction mixture was filtered and then degassed yielding a strong yellow solution. 19 All solutions were prepared approximately 30 min before addition of [ 11 C]methyl iodide.…”

“…[ 11 C]Cetrozole synthesized in DMF solution was purified using ACE 5 SuperC18 5 μm (10 Â 150 mm) with acetonitrile in 8.1 mM ammonium carbonate solution (40/60) as eluent. 19 [ 11 C]UCB-J was purified using a Phenomenex Gemini 5 μm NX-C18 (250 Â 10 mm) column eluted with acetonitrile in AMF buffer (pH 10) (40/60). The preparative UV and radioactivity chromatograms of all the 11 C-labeled compounds are found in Figures S1-S6.…”

“…Analysis of residual palladium in the isolated product was not performed but it can be noted that our previous studies have only showed extremely low amounts. 5,19 The Suzuki-type coupling reaction with [ 11 C]methyl iodide is a multistep process where a 11 C-methyl palladium complex is formed by oxidative addition, the complex reacts with the organoborane precursor in a transmetalation step and finally the 11 C-labeled product is released by reductive elimination (Figure 2A). 18,20,21 The organoborane compound enters in transmetallic step in the form of a boronic acid.…”