ANSTO delivers new medical radioisotope

Health researchers at ANSTO, in collaboration with diverse teams across the organisation, have successfully undertaken preclinical imaging experiments using an important medical isotope, terbium-161 (Tb-161), produced for the first time in Australia by ANSTO in the OPAL multi-purpose reactor. 
 

Terbium-161 is an emerging therapeutic radioisotope with attractive properties for personalised cancer treatment. 
 

A major application being explored across Australia and worldwide is in prostate cancer treatment, where radiopharmaceuticals that bind to the protein PSMA are well-established for providing targeted internal radiotherapy. 

This project developed a pipeline at ANSTO to use OPAL-produced Tb-161 in research applications. The process comprised isolating and purifying Tb-161, conjugating the radioisotope to a PSMA-targeting drug to produce a clinically relevant radiopharmaceutical, and testing it using a prostate cancer laboratory model.  
 

“It is a significant scientific achievement, demonstrating the expertise of ANSTO researchers to produce, purify and deliver a radioisotope for advanced imaging and potential use in treating cancer,” said Dr John Bennett, Co-Director, Health Research & Technology Group.   

The development of the pipeline 

Fit-for-purpose automation technologies were designed, built and optimised to ensure the safe and reliable processing of the irradiated targets. 
 

After the targets were retrieved from the reactor by the OPAL and Nuclear Medicine teams, they were handed over to the Health group in sealed ampoules for processing of the radioactive materials.  
 

The terbium-161 then had to be separated from the bulk gadolinium oxide (Gd₂O₃) by chemical processes. 
 

Once the terbium-161 was extracted, it was converted into terbium-161 chloride ([¹⁶¹Tb]TbCl₃, a form suitable for use in radiolabelling to produce radiopharmaceuticals. 
 

“A critical requirement in the processing was to ensure there could be no skin contamination by the irradiated powder during the opening of the ampoules,” said Dr Paul Pellegrini, Principal Radiochemist in the Radioisotopes team and project supervisor. 
 

“We used in-house designed and built automation equipment at this stage to minimise the contamination risk.” 
 

Further separation of the terbium-161 from by-products was supported by the use of remotely operated production modules, enabling the scale-up to useful preclinical quantities. 
 

“To be able to provide sufficient quantities of Tb-161 for this type of study, many inputs were required.  Expertise was needed in neutron irradiation, chemical processing, automated module development and radiation protection to produce the radioisotope in a safe and sustainable manner,” said Mr Andrew Winthorpe, Radioisotopes Manager.  
 

Further automation was required to attach Tb-161 to the PSMA-targeting drug before the radiopharmaceutical was passed to the Biology and Preclinical Imaging team. 
 

Researchers administered it to laboratory animals that had been implanted with human prostate cancer cells with the assistance of the Vivarium team.  The animals were then scanned on a dedicated small-animal SPECT camera to test whether the radiopharmaceutical would be able to target cancer in the living animal. 
 

SPECT images detect gamma-ray emissions to provide detailed information about the time course of radiation dose to healthy and tumour tissues. The high-resolution scans confirmed that the ¹⁶¹Tb-labelled PSMA drug was selectively taken up at the tumour site and cleared out of the animal’s body through the kidneys and bladder. 

The teams are now preparing to expand the research program. ¹⁶¹Tb-labelled treatments will be compared with other cancer treatment methods, the effectiveness of new ¹⁶¹Tb-labelled radiopharmaceuticals will be evaluated, and potential strategies to improve patient treatment will be developed.