Last-Step Pd-Mediated [¹¹C]CO Labeling of a Moxestrol-Conjugated o-Iodobenzyl Alcohol: From Model Experiments to in Vivo Positron Emission Tomography Studies

Abstract

The fast, efficient, and functional group tolerant last-step radiolabeling of bioconjugates is crucial for positron emission tomography (PET) applications. In this context, o-iodobenzyl alcohol based structures were identified as ideal tags for an easy Pd-catalyzed carbonylation after bioconjugation, and a moxestrol-conjugated precursor was chosen as the model compound for the further studies. Despite scale and time constraints, conditions developed with [C]CO and [C]CO were easily transferred to the C isotope, and the desired radioactive product was obtained in amounts up to 740 MBq with radiochemical purities higher than 99%. Radio-high-performance liquid chromatography analyses of rat blood samples demonstrated excellent in vivo stability within the time of the acquisition. MicroPET-magnetic resonance imaging showed excretion pathways similar to moxestrol, and molecular modeling was also performed to evaluate the potential ability of this conjugate to bind estrogen receptors α. Thus, being both synthetically and biologically suitable, this strategy clears the path to potential novel biotracers for preclinical PET imaging.

Reactive Palladium–Ligand Complexes for 11C-Carbonylation at Ambient Pressure: A Breakthrough in Carbon-11 Chemistry

“…Two molecules of biological interest were labeled in this study: (i) moxestrol, a steroid ligand with a specificity for the estrogen receptor (ER); and (ii) cyclo-RGD, a cyclopeptide targeting the integrin αvβ3 receptors, which are implicated in different forms of cancer. In a follow-up study, the same group reported the initial evaluation of the [ 11 C]moxestrol conjugate as a potential PET radioligand for the in vivo visualization of ERs [ 57 ]. Unfortunately, no specific binding was detected in vivo using PET−MRI imaging.…”

Application Progress of Silyl Carboxylic Acid in Organic Synthesis

“…作者实现了糖类、生物素、核苷和环 状蛋白等多种生物分子的偶联, 并用化学计量的 13 C 进 行了良好的标记(Scheme 13). 年, 该课题组 [36] 利用 同样的策略合成了 13 CO 标记的莫克雌醇衍生物, 该化 合物在雌鼠体内具有极好的稳定性. 2019 年, Hermange 课题组 [37] 以三苯基膦为配体, 使 图式 13 硅基羧酸释放 CO 用于示踪剂的合成 Scheme 13 Tracer synthesis with CO released from silicic acid 13 C 标记的硅基羧酸作为 13 CO 源, 将该络合物与 13 CO 用于制备各种内酯化合物(75) (Scheme 14).…”