Alpha-SPECT: Hyperspectral single photon imaging of targeted α-emission therapy

311 Objectives: Targeted alpha-emitter therapies (TATs) are an important modality in the cancer therapy arsenal [1-3]. Estimating TAT dose distribution plays a critical role in understanding the targeting behavior and dose response and is typically measured using nuclear medicine imaging. However, several significant challenges include low administered activity and complex decay schemes and gamma-ray energy spectra. Moreover, some radionuclides have daughters with significant half-lives and thus the potential to redistribute in the body. To address these issues, we have designed a special purpose system, Alpha-SPECT, that uses state-of-art spectroscopic CZT detectors [4] and a synthetic compound eye camera design [5] to offer excellent spatial resolution, ultrahigh sensitivity, and superior energy resolution to facilitate hyperspectral single (gamma ray) photon imaging (HSPI) of internal alpha emitters and their daughters in large animals. Methods: The design of the Alpha-SPECT system is based on a hyperspectral CZT detector module (Fig.A2). Each 5-mm thick CZT crystal has an active area of 2 cm × 2 cm, bump-bonded to a HEXITEC ASIC with 40 × 40 pixels of 500 μm ×500 μm pitch [4]. The HEXITEC CZT detector provides an excellent energy resolution and an adequate sensitivity across a wide energy range of 0-500 keV (sub-1 keV below 100 keV, 1-2.5 keV for 100-250 keV, and 2.5-5 keV for 250-500 keV), which is ideally suited for imaging gamma rays of 100-450 keV emitted from 225Ac, 223Ra, 227Th, and 212Pb and their daughters. The Alpha-SPECT system is a cylindrical partial-ring of roughly 48 cm diameter by 24 cm axial length. It consists of 7 camera panels, each having a 5 × 10 array of CZT detector modules (Fig.A1) [6], for a total active area of 1400 cm2. The system covers 270° around the object and offers an open bore of 40 cm in diameter. The design shows an opening of around 30 cm in width on the bottom side, which allows for a flexible gantry access and to accommodate oversized objects (Fig.B1-B2). Within Alpha-SPECT, each detector module is coupled to an aperture for a total of 350 independent micro-camera-elements that can be individually optimized to offer a desired combination of spatial resolution, detection efficiency, and field-of-view (FOV). Results: Experimental studies. We have carried out an extensive set of experimental studies to evaluate the spectroscopic performance of the HEXITEC CZT and CdTe detectors of 1 mm to 5 mm thicknesses. Fig. C2 shows a measured energy resolution using a 1-mm CdTe detector and a multi-isotope liquid source containing 99mTc, 201Tl, 123I, and 111In, and demonstrates an excellent energy resolution across 30-300 keV. All major gamma ray lines are clearly separated, which makes it ideally suited for quantitative extraction of the contributions from the characteristic gamma rays emitted by the therapeutic alpha emitters. The histogram in Fig. C2 shows the measured energy resolution values across 40 × 40 pixels on a 5-mm CZT detector with an average resolution of 1.5 keV. Monte Carlo studies. We have carried out detailed Monte Carlo simulations to demonstrate that the proposed Alpha-SPECT design can achieve a geometrical peak sensitivity of ~0.2% due to a remarkable density of angular sampling. The system design provides also an imaging resolution of 2-4 mm in an extended FOV of 20 cm in diameter, tailoring large animal applications (rabbits, pigs, monkeys) that are important in preclinical TAT development. Conclusions: HSPI has substantial potential for the clinical application in TAT. The observed energy resolution and the ability to image multiple isotopes are important for reducing the effects of scatter and enables quantitative SPECT of alpha emitters and their daughters. The proposed system would provide the ability to perform quantitative SPECT of multiple isotopes with closely spaced gamma ray lines and the flexibility of tailoring the FOV, sensitivity and imaging resolution for either organ-specific or whole-body assessment of the TATs.