Human Absorbed Dose Evaluation of [¹⁷⁷Lu]Lu-IBA as a Bone Palliative Candidate

Abstract

The role of lutetium-177 among bone-seeking radionuclides in targeted therapy is noteworthy. The clinical pharmacokinetics of ibandronate (IBA) indicates that this bisphonate has powerful bone mineral affinity. The aim of this study was to evaluate of [¹⁷⁷Lu]Lu-IBA efficacy as a new compound.

The [¹⁷⁷Lu]Lu-IBA was prepared by radiolabeling of IBA ligand to ¹⁷⁷LuCl3 that was obtained by thermal neutron irradiation of enriched Lu2O3 sample. Produced [¹⁷⁷Lu]Lu-IBA with high radiochemical purity was administered intravenously to mice. Biodistribution data were collected at 1, 4, 24, 48 h and 7 d post injections. With calculating accumulated activities in each organ and extrapolating mouse’s organs to human’s organs by the RADAR method and using OLINDA/EXM software the injected dose in various human organs was achieved.

[¹⁷⁷Lu]Lu-IBA was produced with radiochemical purity nearly 96 %. Its biodistribution data showed the high uptake and durability in the skeletal tissues without significant uptake in other major organs.

The results showed that [¹⁷⁷Lu]Lu-IBA has considerably good properties as a bone-seeking radiopharmaceutical and therefore can be a candidate for bone pain palliative therapy in skeletal metastases; however, further biological studies are still needed.

Zusammenfassung

Die Rolle von Lutetium-177 unter den knochensuchenden Radionukliden in der zielgerichteten Therapie ist bemerkenswert. Die klinische Pharmakokinetik von Ibandronat (IBA) deutet darauf hin, dass dieses Bisphosphonat eine starke Affinität zu Knochenmineral besitzt. Das Ziel dieser Studie war es, die Wirksamkeit von [¹⁷⁷Lu] Lu-IBA als neue Verbindung zu untersuchen.

[¹⁷⁷Lu] Lu-IBA wurde durch Radiomarkierung des IBA-Liganden an ¹⁷⁷LuCl3 hergestellt, das durch thermische Neutronenbestrahlung einer angereicherten Lu2O3-Probe gewonnen wurde. Hergestelltes [¹⁷⁷Lu] Lu-IBA mit hoher radiochemischer Reinheit wurde Mäusen intravenös verabreicht. Biodistributionsdaten wurden 1, 4, 24, 48 Stunden und 7 Tage nach der Injektion gesammelt. Durch die Berechnung der akkumulierten Aktivitäten in jedem Organ und die Extrapolation der Mäuseorgane auf die Organe des Menschen mittels der RADAR-Methode und unter Verwendung der OLINDA/EXM-Software wurde die injizierte Dosis in verschiedenen menschlichen Organen ermittelt.

[¹⁷⁷Lu] Lu-IBA wurde mit einer radiochemischen Reinheit von fast 96 % hergestellt. Seine Biodistributionsdaten zeigten die hohe Aufnahme und Haltbarkeit im Skelettgewebe ohne signifikante Aufnahme in andere wichtige Organe.

Die Ergebnisse zeigten, dass [¹⁷⁷Lu] Lu-IBA als knochensuchendes Radiopharmazeutikum beträchtlich gute Eigenschaften aufweist und daher ein Kandidat für eine palliative Knochenschmerztherapie bei Skelettmetastasen sein kann. Weitere biologische Studien sind jedoch noch erforderlich.

Keywords

¹⁷⁷Lu-IBA - bone metastases - internal dosimetry - RADAR - OLINDA/EXM - nitrogen containing bisphosphonates

Schlüsselwörter

¹⁷⁷ Lu-IBA - Knochenmetastasen - interne Dosimetrie - RADAR - OLINDA/EXM - stickstoffhaltige Bisphosphonate

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