TY - JOUR T1 - <strong>An Ultrahigh Energy Resolution SPECT System for Quantitative Hyperspectral Imaging of Targeted Alpha Therapy</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 3305 LP - 3305 VL - 63 IS - supplement 2 AU - Ling Cai AU - Elena Maria Zannoni AU - Ling Jian Meng Y1 - 2022/06/01 UR - http://jnm.snmjournals.org/content/63/supplement_2/3305.abstract N2 - 3305 Introduction: Targeted radionuclide therapy (TRT) shows great efficacy in malignancies treatment as it delivers concentrated dose to tumor site without damaging the surrounding healthy tissues. Targeted alpha therapy (TAT) is the most advantageous TRT approach that induces localized cytotoxic effects due to high linear energy transfer (LET) and short range (50-100 &lt;m:omath&gt;&lt;m:rpr&gt;&lt;m:scr m:val="roman"&gt;&lt;m:sty m:val="p"&gt;&lt;/m:sty&gt;&lt;/m:scr&gt;&lt;/m:rpr&gt;μm&lt;/m:omath&gt;) of &lt;m:omath&gt;α&lt;/m:omath&gt; -particles [1]. However, the migration of daughter products with long half-lives increases unknown toxicity to non-target organs [2-3]. Therefore, TAT would benefit from more investigation into micro-dosimetry and quantitative imaging. This will allow to understand the fate of both parent and progeny, thus optimize efficacy and enhance safe clinical implementation.The main challenges in imaging alpha-emitters include very low administered activities and complex decay schemes producing densely populated gamma-ray energy spectra. Therefore, nuclear imaging instrumentation with excellent energy resolution is required to perform simultaneous multi-isotope imaging, to reduce interferences from scattering, and to improve the overall quantitative accuracy.We have fully developed an ultrahigh energy-resolution spectral SPECT imaging system for preclinical applications, the Alpha-SPECT-mini. We will present (a) the system design based on 24 CdTe imaging spectrometers and a multi-channel readout circuitry [4], and (b) the multi-isotope and multi-functional imaging capability of the system for mapping therapeutic alpha emitters, such as Ac-225 and Ra-223, and their daughters in quantitative small-animal phantoms.Methods: &lt;u&gt;Alpha-SPECT-mini system design&lt;/u&gt;&lt;u&gt;:&lt;/u&gt; Fig.1A-B show the system constructed by 6 detector panels arranged in a hexagonal stationary gantry. Each detector panel consists of a &lt;m:omath&gt;2×2&lt;/m:omath&gt; array of detector modules (Fig.1E). Each CdTe detector module is &lt;m:omath&gt;&lt;m:scr m:val="roman"&gt;&lt;m:sty m:val="p"&gt;&lt;/m:sty&gt;&lt;/m:scr&gt;&lt;/m:rpr&gt;20 mm×20 mm×1 mm&lt;/m:omath&gt; in size. The detector ring is then coupled with a 14-mm thick collimator aperture that has 96 knife-edge pinholes (Fig.1C-D). Each pinhole is 1 mm in diameter and projects a view of the object volume on a non-overlapping subdetector active area (&lt;m:omath&gt;&lt;m:scr m:val="roman"&gt;&lt;m:sty m:val="p"&gt;&lt;/m:sty&gt;&lt;/m:scr&gt;&lt;/m:rpr&gt;1 cm×1 cm&lt;/m:omath&gt;). Results: In our preliminary studies, we present the spectral response of a single CdTe detector module using Ac-225-(Fig.1F) and Ra-223- (Fig.1G) filled phantoms. As visible, the detector ultrahigh energy resolution allows to fully resolve the main photopeaks from Ra-223, Ac-225 and their daughters, and to capture and distinguish also secondary energy peaks, Kα and Kβ fluorescence X-rays and escape peaks in a broad energy range 20-450 keV.To demonstrate the hyperspectral capabilities of the Alpha-SPECT-mini system, we performed a multi-isotope imaging study where a phantom (Fig.1H) contained five clinically relevant radioisotopes, namely I-125, Tc-99m, In-111, Tl-201 and I-123. The spectra of two pixels are shown in Fig.1I. By selecting narrow energy windows around the radioisotopes’ photopeaks, the spatial distribution of the five different isotopes is shown in Fig.1J. From the planar images of Tl-201 acquired for 10, 6.7, 3.3 and 0.7 seconds (Fig.1K-L), we performed an initial detection limit assessment. In a 30 min acquisition, the system can potentially detect activities lower than &lt;m:omath&gt;18.3 &lt;m:scr m:val="roman"&gt;&lt;m:sty m:val="p"&gt;&lt;/m:sty&gt;&lt;/m:scr&gt;&lt;/m:rpr&gt;nCi&lt;/m:omath&gt; of Ra-223 using its 80-85 keV emission peaks, while maintaining a SNR value of 6.13. Additionally, reducing the width of the energy window from 15 keV to 5 keV improves the SNR (Fig.1K-L), which demonstrates the benefit of a superior energy resolution for quantitative multi-isotope SPECT imaging studies.Conclusions: The Alpha-SPECT-mini system offers an unprecedented energy resolution of &lt;2 keV at 140 keV, and an excellent sensitivity due to the 96-pinhole non-multiplexing collimator design. It will allow to quantify distributions from multiple isotopes, to improve the image SNR and to lower the minimum activity required. The system will be an ideal platform for imaging alpha-emitters and their daughters having gamma-ray emissions within the lower and medium energy range of 60-250&lt;m:omath&gt; &lt;m:rpr&gt;&lt;m:scr m:val="roman"&gt;&lt;m:sty m:val="p"&gt;&lt;/m:sty&gt;&lt;/m:scr&gt;&lt;/m:rpr&gt;keV&lt;/m:omath&gt;. ER -