RadChem 2018

Production of Lutetium-177 via a solvent extraction based Lu-177m/Lu-177 radionuclide generator

14 May 2018, 16:30

15m

Red Hall (Casino Conference Centre)

Verbal Separation Methods, Speciation SEP 1

Speaker

Mrs Rupali Bhardwaj (TU Delft)

Description

Lutetium-177 (¹⁷⁷Lu) is a radionuclide with tremendous potential in radionuclide therapy. ¹⁷⁷Lu based pharmaceuticals are applied in neuroendocrine tumour treatment and have been approved for prostate cancer treatment. We have proposed the idea of a ^177mLu/¹⁷⁷Lu radionuclide generator for 177Lu production based on the separation of the daughter nuclei, ¹⁷⁷Lu from its parent nuclei, ^177mLu [1]. It was followed by the proof of concept using a reversed phase chromatographic system [2]. In our work, ^177mLu-DOTA-(Tyr3)-octreotate (DOTATATE) complex was retained on tC-18 silica and the bond ruptured ¹⁷⁷Lu ions was collected using a mobile phase flow. Using this method of separation, ¹⁷⁷Lu/ ^177mLu activity ratios were increased from 0.25 (in equilibrium) to values around 250. The ¹⁷⁷Lu was collected with efficiencies of about 65%. However in order to meet the clinical demands ¹⁷⁷Lu/^177mLu activity ratios close to 10,000 is needed. In our current research we are exploiting the potential of solvent extraction in separating the two isomers.
In solvent extraction, ^177mLu is complexed with different chelating agents such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), DOTA-(Tyr3)-octreotate (DOTATATE) and others. The aqueous solution of complexed ^177mLu is left at a fixed temperature for a fixed interval of time to allow the accumulation of ¹⁷⁷Lu. After the fixed accumulation period, it is stirred with an immiscible organic phase (dihexyl ether) containing an extracting agent, Di-(2-ethylhexyl)phosphoric acid (DEHPA) to collect the free ¹⁷⁷Lu, as shown in figure 1. Using this method of separation we are able to achieve ¹⁷⁷Lu/^177mLu activity ratios close to 3000, with a ¹⁷⁷Lu collection efficiency close to 50%.
By optimizing the extraction process and by utilizing a microfluidic device we aim to deliver a system able to reach the quality needed for medical applications and to provide with a generator with ease of use that can provide with lutetium-177 for long periods of time on location.
1. De Vries, D.J. and H. Wolterbeek, The production of medicinal 177Lu and the story of 177mLu: detrimental by-product or future friend? Tijdschr. Nucl. Geneeskd, 2012. 34: p. 899-904.
2. Bhardwaj, R., et al., Separation of nuclear isomers for cancer therapeutic radionuclides based on nuclear decay after-effects. Scientific Reports, 2017. 7: p. 44242.