Synthesis and radiochemical stability evaluation of radiopharmaceutical compounds containing radioiodinated prosthetic groups

[摘要] ENGLISH ABSTRACT:A study was undertaken to investigate the radiochemical stability of the βiodoethoxyl moiety,a relatively novel prosthetic group employed in radiopharmaceutical chemistry, in which anoxygen atom in a β-position relative to the radioiodine atom has a stabilising effect on thealiphatic carbon-iodine bond. The investigation was started as a pilot study by synthesisingvarious model compounds containing a β-radioiodoethoxyl moiety, as well as two referencecompounds lacking such a moiety. The purpose was to determine the influence of variousgroups in the vicinity of the β-oxygen atom on the stability of the abovementioned moiety.Radiochemical stability tests were carried out in vitro at 37°C in human blood serum. Theresults confirmed the superior stability of such a moiety compared to that of the referencecompounds and also showed that the branching of such an aliphatic unit resulted in aconsiderable improvement in its stability, especially over a longer period.The investigation was extended to the synthesis of other compounds containing a few selectedβ-iodoethoxyl moieties that showed improved stability in the pilot study work. Referencecompounds containing the classical iodovinyl unit, as well as those lacking a stabilising β-oxygen atom, were also prepared. The carrier molecules used in this part of the work was abenzamide containing a phenolic oxygen atom which acted as the β-oxygen atom, as well astwo heterocyclic amines, benzotriazole and 2-methyl-5-nitroimidazole, in which the β-iodoethoxyl moiety was linked to a secondary nitrogen atom. Various suitable alkylating agentswere prepared, chemically linked to the carrier molecules, the resulting intermediatecompounds converted into tosylate or triflate iodination precursors and labelled withradioiodine by means of iodide-for-tosylate/triflate exchange. In vitro stability tests of thesecompounds showed similar trends to those obtained with the model compounds. Moreover, thestability of the stabilised β-iodoethoxyl moiety compared favourably with that of the iodovinylunit, especially when incorporated into a heterocyclic amine. The results of this study have shown that some of the radioiodinated compounds synthesized in this work, especially thenitroimidazole derivatives, have the potential to be considered as novel radiopharmaceuticals.

[发布机构] Stellenbosch University