Evaluation of 209At as a theranostic isotope for 211At-radiopharmaceutical development using high-energy SPECT

The development of alpha-emitting radiopharmaceuticals using 211 At requires quantitative determination of the time-dependent nature of the 211 At biodistribution. However, imaging-based methods for acquiring this information with 211 At have not found wide-spread use because of its low abundance of decay emissions suitable for external detection. In this publication we demonstrate the theranostic abilities of the 211 At/ 209 At isotope pair and present the first-ever 209 At SPECT Images. Methods: The VECTor microSPECT/PET/CT scanner was used to image 209 At with a collimator suitable for the 511 keV annihilation photons of PET isotopes. Data from distinct photopeaks of the 209 At energy spectrum (195 keV (22.6%), 239 keV (12.4%), 545 keV (91.0%), a combined 782/790 keV peak (147%), and 209 Po x-rays (139.0%)) were independently evaluated for use in image reconstructions using Monte Carlo (GATE) simulations and phantom studies. 209 At-imaging in vivo was demonstrated in a healthy mouse injected with 10 MBq of free [ 209 At]astatide. Image-based measurements of 209 At uptake in organs of interest - acquired in 5-minute intervals - were compared to ex vivo gamma counter measurements of the same organs. Results: Simulated and measured data indicated that - due to the large amount of scatter from high energy (>750 keV) gammas - reconstructed images using the x-ray peak outperformed those obtained from other peaks in terms of uniformity and spatial resolution, determined to be