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Phys Med Biol. 2018 Jan 25. doi: 10.1088/1361-6560/aaaa95. [Epub ahead of print]

Evaluation of <sup>209</sup>At as a theranostic isotope for <sup>211</sup>At-radiopharmaceutical development using high-energy SPECT.

Author information

1
Molecular Oncology, British Columbia Cancer Research Centre, 675 W 10th Ave, Vancouver, British Columbia, V5Z 1L3, CANADA.
2
Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, V6T 1Z4, CANADA.
3
Life Sciences Division, TRIUMF, Vancouver, British Columbia, CANADA.
4
Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, CANADA.
5
Accelerator Division, TRIUMF, Vancouver, British Columbia, CANADA.
6
Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, CANADA.
7
Department of Physics and Astronomy, University of British Columbia, Hennings Building, 6224 Agricultural Road, Vancouver, BC, V6T 1Z1CANADA, Vancouver, British Columbia, CANADA.
8
Department of Radiology, University of British Columbia, Vancouver, British Columbia, CANADA.
9
TRIUMF, University of British Columbia, 4004 Wesbrook Mall, Vancouver BC, Vancouver, British Columbia, V6T 1W5, CANADA.

Abstract

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

KEYWORDS:

SPECT; astatine-209; astatine-211; preclinical imaging; theranostic pair

PMID:
29369043
DOI:
10.1088/1361-6560/aaaa95

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