Optimized 211At production: a study to unravel the impact of the 210At-contaminant

Aim/Introduction: A limitation to the availability of 211At via209Bi(α,2n) is the restriction of the incident α-beam energyduring production to avoid the co-production of 210At whichdecays predominantly to 210Po. However, recent data measureda significant increase in 211At activity at increased beam energy,highlighting the need for an optimised approach and stressingthe importance of studying the radiochemical separation andthe biodistribution of 210Po after radioligand therapy with211At/210At-labelled radiopharmaceuticals. For this reason,we acquired targets irradiated at high α-beam energies andperformed: (i) the determination of the activity balance of 211At,210At and 210Po after radiochemical separation of astatine byextraction chromatography [1] and (ii) a preclinical feasibility studyto assess the biodistribution of 211At, 210At and 210Po. Materialsand Methods: Targets irradiated by Arronax, Nantes were usedto establish activity balances during radiochemical separation.After dissolution of the target and radiochemical separationby extraction chromatography, astatine was measured bygamma spectrometry, whereas 210Po was determined by liquidscintillation counting. Dissolution yields, extraction yields, andseparation capabilities were assessed. For the preclinical study,irradiated targets were acquired from Rigshospitalet, Copenhagen.After target dissolution and radiochemical separation, anti-HER2sdAb 2Rs15d [2] was labelled with 210At/211At, after which 1 MBq211At was injected in healthy mice. The biodistribution of 211At,210At and 210Po was assessed 1h post tracer injection. Results:Activity balances during target processing and radiochemicalseparation show mean decay-corrected dissolution yields of>84% and extraction yields of 210At/211At >80%. At the sametime,>95% of the 210Po formed before extraction was removed.The biodistributions of 211At, 210At and 210Po in healthy miceshow the highest uptake in the kidneys (60-70% ID/g) whilestomach, small intestine and thyroid range between 2-4% ID/g,the latter ones showing a potentially limited dehalogenation.The time between the end of conjugation and time of sacrificeallowed a total of 0.03% of the 210At activity to be decayed to210Po (1-2 Bq). Kidney measurements after complete decayresulted in a total 210Po activity (0.5 Bq) which is slightly higherthan the expected 0.3 Bq due to the measured 210At at timeof sacrifice and subsequent ingrowth. Conclusion: Our resultsshow that extraction yields are >84% when using extractionchromatography while safely isolating the previously formed210Po. The biodistributions of 211At, 210At and 210Po inhealthy mice indicate a limited impact of 210Po, paving theway towards increased 211At production yield.