Hyperspectral Single Photon Imaging of Targeted Alpha Therapy

1141 Introduction: Targeted alpha therapy (TAT) has been demonstrated to be a highly effective therapeutic modality against disseminated cancer, due to the high linear energy transfer (LET) [1] and the short distance (50-100 μm) travelled by the emitted alpha-particles [2]. The great efficacy of the treatment is challenged by the migration of daughter products following alpha decay [3], the conjugation of radionuclides to antibodies, as well as the unknown toxicities of the decay products [4]. All these issues call for the need of developing a reliable method for quantitative imaging of alpha-emitting radionuclides. This would allow to simultaneously determine the biodistributions of both parent and daughter radionuclides in vivo, and hence to have a thorough understanding of radiopharmaceutical uptake and kinetics for radiotherapeutic applications. However, due to the low administered activity and complex decay schemes, a SPECT imaging system for TAT would require detectors with excellent energy resolution capabilities, to discriminate energy peaks from the different radioisotopes involved and to perform simultaneous multi-isotope acquisitions. In this study, we present a preclinical hyperspectral single photon imaging (HSPI) system for TAT, based on newly developed CdTe detectors [5], a high-performance multi-detector readout circuitry [6], and an innovative Synthetic Compound-Eye (SCE) gamma camera design [7]. In addition, we will present preliminary imaging results of phantoms filled with Ra-223 and other clinically relevant alpha emitters. Methods: The System Design: The HSPI system is constructed by six detector panels, arranged in a hexagonal stationary gantry, with a total active detection area of 96 cm2 (Fig.1A). The distance between the surfaces of two opposite detectors is 80 mm (Fig. 1B). The system in then equipped with a collimator aperture that contains 96 knife-edge pinholes, (72x) 500 μm and (24x) 1 mm in diameter with different minification factors (Fig.1C-D), according to the SCE geometry [7]. The solid-state detector: Each detector panel consists of a 2×2 array of CdTe modules (Fig.1E). Each 1-mm thick CdTe crystal offers an active area of 20 mm × 20 mm, bump-bonded to a High Energy X-ray Imaging TEChnology (HEXITEC) ASIC with 80 × 80 pixels of 250 μm ×250 μm pitch [5] (Fig.1F). Each detection unit will offer an excellent spatial resolution (250 μm) and an unprecedented energy resolution (0.76% ± 0.14 FWHM at 140 keV) in a broad dynamic energy range (4-600 keV). The ultra-high energy resolution offered by the detectors is preserved by the high-speed multi-detector readout circuitry recently developed by our group [6]. Preliminary Results: Fig.1G shows an energy spectrum of Am-241 and Co-57 sources measured with a single 1-mm CdTe detector. We also recorded the spectral response of 60-μCi Ac-225 water solution in a 5-cm-diameter spherical volume, which was placed in a water filled torso phantom (Fig.1H). Fig.1I shows the acquired energy spectrum in comparison with the one obtained by a clinical SPECT/CT system (Siemens Symbia Intevo). The excellent energy resolution of the HSPI detection system allowed us to resolve and to quantify the gamma ray contributions from Ac-225 (100 keV and 150 keV), and its daughters, such as Fr-221 (218 keV) and Bi-213 (440 keV). Conclusions: We have developed a hyperspectral single photon imaging system for preclinical applications. The system offers an unprecedented energy resolution and an excellent sensitivity to perform quantitative SPECT imaging of multiple isotopes with closely spaced gamma ray peaks. This study will further discuss how the enhanced spatial-spectral capability is translated into an improved imaging performance. We believe this system will provide invaluable information on the multi-isotope pharmacokinetics and toxicity of TAT under in vivo pre-clinical studies. Acknowledgements We acknowledge the support from NIH/NIBIB as funding agency (grants R01 EB022388-01 and R01 EB026300-01A1).