Sci-Thur AM: YIS – 01: New technologies for astatine-211 targeted alpha therapy research

Authors


Abstract

Purpose:

The short-range, densely ionizing α-particles emitted by 211At (t1/2=7.2h) are well suited for the treatment of diffuse microscopic disease, using cancer targeting biomolecules. 211At availability is limited by the rarity of α-cyclotrons required for standard production. Image-based dosimetry is also limited for 211At, which emits low intensity X-rays. Our goal was to leverage state-of-the-art infrastructure at TRIUMF to produce and evaluate two related isotopes, 211Rn (t1/2=14.6h, 73% decay to 211At) as a generator for 211At, and 209At (t1/2=5.4h, X-ray/gamma-ray emitter) as a novel 211At surrogate for preclinical imaging studies.

Methods:

Produced by spallation of uranium with 480 MeV protons, mass separated ion beams of short-lived francium isotopes were implanted into NaCl targets where 211Rn or 209At were produced by radioactive decay, in situ. 211Rn was transferred to dodecane from which 211At was efficiently extracted and evaluated for clinical applicability. High energy SPECT/CT was evaluated for measuring 209At activity distributions in mice and phantoms.

Results:

Our small scale 211Rn/211At generator system provided high purity 211At samples. The methods are immediately scalable to the level of radioactivity required for in vivo experiments with 211At. 209At-based high energy SPECT imaging was determined suitable for pursuing image-based dosimetry in mouse tumour models. In the future, we will utilize quantitative 209At-SPECT for image-based dose calculations.

Conclusion:

These early studies provided a foundation for future endeavours with 211At-based α-therapy. Canada is now significantly closer to clinical targeted α-therapy of cancer.

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