Evaluation of²⁰⁹At as a theranostic isotope for²⁰⁹At-radiopharmaceutical development using high-energy SPECT

Abstract

The development of alpha-emitting radiopharmaceuticals using ²¹¹At requires quantitative determination of the time-dependent nature of the ²¹¹At biodistribution. However, imaging-based methods for acquiring this information with ²¹¹At 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 ²¹¹At/²⁰⁹At isotope pair and present the first-ever ²⁰⁹At SPECT images. The VECTor microSPECT/PET/CT scanner was used to image ²⁰⁹At with a collimator suitable for the 511 keV annihilation photons of PET isotopes. Data from distinct photopeaks of the ²⁰⁹At energy spectrum (195 keV (22.6%), 239 keV (12.4 %), 545 keV (91.0 %), a combined 782/790 keV peak (147 %), and ²⁰⁹Po x-rays (139.0 %)) were independently evaluated for use in image reconstructions using Monte Carlo (GATE) simulations and phantom studies. ²⁰⁹At-imaging in vivo was demonstrated in a healthy mouse injected with 10 MBq of free [²⁰⁹At]astatide. Image-based measurements of ²⁰⁹At uptake in organs of interest-acquired in 5 min intervals-were compared to ex vivo gamma counter measurements of the same organs. 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 image uniformity and spatial resolution, determined to be <0.85 mm. ²⁰⁹At imaging using the x-ray peak revealed a biodistribution that matched the known distribution of free astatide, and in vivo image-based measurements of ²⁰⁹At uptake in organs of interest matched ex vivo measurements within 10%. We have acquired the first ²⁰⁹At SPECT images and demonstrated the ability of quantitative SPECT imaging with ²⁰⁹At to accurately determine astatine biodistributions with high spatial and temporal resolution.