Endocrine Abstracts

A new radiopharmaceutical using the somatostatin analogue octreotide has been developed for use in humans. SARTATE consists of the novel bifunctional chelator, MeCOSar, conjugated to (Tyr³)-octreotate. MeCOSar is a superior chelator for copper over a wide pH range and at room temperature, which allows for SARTATE to be used as an imaging/therapy pair when radiolabelled with copper-64 and copper-67.

⁴Cu-SARTATE was produced by radiolabelling SARTATE (AusPep, Victoria) with cyclotron-generated copper-64-chloride (Sir Charles Gairdner Hospital, Western Australia). Previous pre-clinical development work had shown that ⁶⁴Cu-SARTATE was stable in vivo (Paterson et al., 2014). Experiments were then undertaken to adapt the pre-clinical manual radiolabelling method for use in humans, which aimed to optimise conditions for reaction time, temperature, ligand amount, column cartridge purification and the use of quench agents to limit radiolysis. Four validation studies, requiring full quality control per production, were performed on the final method. Ten productions were made for human clinical PET/CT imaging. The production yield for each synthesis was calculated to monitor the performance and efficiency of the synthesis. The radiochemical purity of the final product was assessed by HPLC.

Discussion: ⁶⁴Cu-SARTATE had shown it was susceptible to radiolysis at activity levels required for human imaging. This required optimisation of the HPLC analysis to separate and quantify radiolysis products – which could not be accurately assessed by TLC. Several stability studies looking at the addition of quench agents to limit radiolysis were then carried out. ⁶⁴Cu-SARTATE was ultimately prepared by radiolabelling for 30 min at room temperature, followed by SPE using a C18 cartridge. The susceptibility to radiolysis was overcome through the use of quench agents.

Conclusion: A consistent and reliable non-automated method for producing ⁶⁴Cu-SARTATE for clinical trials was developed, and successfully used in a Phase 1 clinical trial of ten patients.

Reference

1. Paterson, B., Roselt, P., Denoyer, D., Cullinane, C., Binns, D., Noonan, W., Jeffery, C., Price, R., White, J., Hicks, R. and Donnelly, P. (2014). PET imaging of tumours with a 64 Cu labeled macrobicyclic cage amine ligand tethered to Tyr 3-octreotate. Dalton Trans., 43(3), pp.1386-1396.