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 . It was followed by the proof of concept using a reversed phase chromatographic system . 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.
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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.