Syntheses of [21-11C] and (21-13C) progesterone

Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds

“…Two pathways were developed for the synthesis of [21-11 C]progesterone. 688,689 The first method employed [ 11 C]CH 3 I as a radiolabeling agent and a p-toluenesulfonylmethyl isocyanide derivative of progesterone (Figure 147) as the precursor. The precursor was initially dissolved in aqueous NaOH, followed by 688 The second radiolabeling pathway proceeded with the aid of [ 11 C]methyl(2-thienyl)cuprate as a synthon which was synthesized from [ 11 C]CH 3 I by initial conversion to [ 11 C]CH 3 Li with an excess of n-BuLi and subsequent reaction with lithium(2-thienyl)cyanocuprate (Figure 147).…”

“…Following these hypotheses, the labeling of a carbon-11 analogue of progesterone was proposed as a viable alternative for cancer imaging. Two pathways were developed for the synthesis of [ 21 - 11 C]­progesterone. , The first method employed [ 11 C]­CH 3 I as a radiolabeling agent and a p -toluenesulfonylmethyl isocyanide derivative of progesterone (Figure ) as the precursor. The precursor was initially dissolved in aqueous NaOH, followed by [ 11 C]­CH 3 I delivery and the radiolabeling at 100 °C for 15 min.…”

“…The precursor 4 -androsten- 3 -one- 5 -ene- 17 -carboxylic acid chloride was synthesized starting from desoxycortisone by oxidation to 4 -androsten- 3 -one- 5 -ene- 17 -carboxylic acid and functionalization to its acyl chloride analogue with oxalyl chloride (Figure ). The 11 C-labeling was then performed via cross-coupling of LiCN and 4 -androsten- 3 -one- 5 -ene- 17 -carboxylic acid chloride in THF at 50 °C in the presence of trimethylsilyl chloride (TMSCl) (Figure ). [ 21 - 11 C]­Progesterone was obtained with an isolated RCY of 30–35% (based on [ 11 C]­CH 3 I initial activity) within 35 min from EOB and A m of 14 GBq/μmol …”

“… The 11 C-labeling was then performed via cross-coupling of LiCN and 4 -androsten- 3 -one- 5 -ene- 17 -carboxylic acid chloride in THF at 50 °C in the presence of trimethylsilyl chloride (TMSCl) (Figure ). [ 21 - 11 C]­Progesterone was obtained with an isolated RCY of 30–35% (based on [ 11 C]­CH 3 I initial activity) within 35 min from EOB and A m of 14 GBq/μmol …”

Cross-Coupling Reactions as Valuable Tool for the Preparation of PET Radiotracers

“…In 1997, Lidström and co-workers used the novel developed lithium [ 11 C]methyl(2-thienyl)cuprate ( 53 ) in order to produce [21- 11 C]-labeled progesterone 54 for its application in in vitro and in vivo PET studies [73]. The required cuprate 53 was synthesized via an exchange reaction of n -BuLi with [ 11 C]methyl iodide, followed by the addition of lithium(2-thienyl)cyanocuprate.…”