Examination of the complexation ability of different calixarene derivatives towards [²²³Ra]RaCl₂ in a hospital radiopharmaceutical laboratory

Summary

Aim: In this contribution we investigated the potential transfer of an established method for the synthesis of ²²³Ra-labelled calixarene complexes to a hospital radiopharmaceutical environment. For this purpose, commercially available [²²³Ra]RaCl₂ solution in pharmaceutical grade (Xofigo^®) was reacted with three calixarene derivatives. Methods: A wellestablished two-phase extraction method using a two-phase solvent system was performed for complexation of the radium ions with calixarenes under slightly basic conditions. Moreover, the complexation reaction was conducted in homogenous medium (water / THF) as well as under elevated temperature. Results: The investigated reaction conditions did not allow the isolation of the desired products. Analytical evidence for the presence of radium-calixarene species by means of activity measurement, TLC as well as HPLC could not been proven unambiguously. Conclusion: We address the non-conversion of the educts to the large excess of sodium ions in the used Xofigo^® solution, what may explain the hampered reaction for all conducted experiments. Finally the transfer of the published complexation concept into a radiopharmaceutical routine environment was not successful.

Zusammenfassung

Ziel: Ziel der vorliegenden Arbeit ist es, eine bekannte Methode zur Synthese von ²²³Ramarkierten Calixaren-Komplexen zunächst auf ihre Reproduzierbarkeit zu prüfen und gegebenenfalls für die Anwendung in einem radiopharmazeutischen Arbeitsbereich einer Klinik zu adaptieren. Als Ausgangsnuklid wurde kommerziell verfügbares [²²³Ra]RaCl₂ in pharmazeutischer Qualität (Xofigo^®) eingesetzt. Dieses wurde mit verschiedenen Calixarenderivaten umgesetzt. Methoden: Die Komplexierungsreaktion wurde sowohl mittels einer in der Literatur beschriebenen Zwei-Phasen-Extraktion als auch in einem homogenen Lösungsmittelgemisch (THF/Wasser) bei schwach basischen Bedingungen durchgeführt. Weiterhin wurde die Reaktionstemperatur variiert. Resultate: Bei keiner der durchgeführten Umsetzungen konnte die Bildung des postulierten Produkts durch spezifische Analysenmethoden wie Aktivitätsmessung, Radio-Dünnschichtchromatographie-Scans sowie Hochleistungsflüssigkeitschromatographie (HPLC) nachgewiesen werden. Schlussfolgerungen: Das Ausbleiben der Komplexierung ist wahrscheinlich auf den extrem hohen Überschuss an Natriumionen in der verwendeten Xofigo^®-Lösung zurückzuführen. Die Anwendung der publizierten Komplexierungsmethode in einem radiopharmazeutischen Kliniklabor ist nicht möglich.

Keywords

Radium dichloride - Calixarene

Schlüsselwörter

Radiumdichlorid - Calixaren

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