In vivo imaging of ²²⁵Ac is a major challenge in the development of targeted alpha therapy radiopharmaceuticals due to the extremely low injected doses. In this paper, we present the design of a multi-modality gamma camera that integrates both proximity and Compton imaging in order to achieve the demanding sensitivities required to image ²²⁵Ac with good image quality. We consider a dual-head camera, each of the heads consisting of two planar cadmium zinc telluride detectors acting as scatterer and absorber for Compton imaging, and with the scatterer practically in contact with the subject to allow for proximity imaging. We optimize the detector's design and characterize the detector's performance using Monte Carlo simulations. We show that Compton imaging can resolve features of up to 1.5 mm for hot rod phantoms with an activity of 1 μCi, and can reconstruct 3D images of a mouse injected with 0.5 μCi after a 15 minutes exposure and with a single bed position, for both ²²¹Fr and ²¹³Bi. Proximity imaging is able to resolve two 1 mm-radius sources of less than 0.1 μCi separated by 1 cm and at 1 mm from the detector, as well as it can provide planar images of ²²¹Fr and ²¹³Bi biodistributions of the mouse phantom in 5 minutes.

Water-based liquid scintillators (WbLS) present an attractive target medium for large-scale detectors with the ability to enhance the separation of Cherenkov and scintillation signals from a single target. This work characterizes the scintillation properties of WbLS samples based on LAB/PPO liquid scintillator (LS). X-ray luminescence spectra, decay profiles, and relative light yields are measured for WbLS of varying LS concentration as well as for pure LS with a range of PPO concentrations up to 90 g L-1. The scintillation properties of the WbLS are related to the precursor LAB/PPO: starting from 90 g L-1PPO in LAB before synthesis, the resulting WbLS have spectroscopic properties that instead match 10 g L-1 PPO in LAB. This could indicate that the concentration of active PPO in the WbLS samples depends on their processing.

Background

Single photon emission computed tomography (SPECT) is an imaging modality that has demonstrated its utility in a number of clinical indications. Despite this progress, a high sensitivity, high spatial resolution, multi-tracer SPECT with a large field of view suitable for whole-body imaging of a broad range of radiotracers for theranostics is not available.

Purpose

With the goal of filling this technological gap, we have designed a cadmium zinc telluride (CZT) full-ring SPECT scanner instrumented with a broad-energy tungsten collimator. The final purpose is to provide a multi-tracer solution for brain and whole-body imaging. Our static SPECT does not rely on the dual- and the triple-head rotational SPECT standard paradigm, enabling a larger effective area in each scan to increase the sensitivity. We provide a demonstration of the performance of our design using a realistic model of our detector with simulated body-sized phantoms filled with ^99m Tc and ¹⁷⁷ Lu.

Methods

We create a realistic model of our detector by using a combination of a Geant4 Application for Tomographic Emission (GATE) Monte Carlo simulation and a finite element model for the CZT response, accounting for low-energy tail effects in CZT that affects the sensitivity and the scatter correction. We implement a modified dual-energy-window scatter correction adapted for CZT. Other corrections for attenuation, detector and collimator response, and detector gaps and edges are also included. The images are reconstructed using the maximum-likelihood expectation-maximization. Detector and reconstruction performance are characterized with point sources, Derenzo phantoms, and a body-sized National Electrical Manufacturers Association (NEMA) Image Quality (IQ) phantom for both ^99m Tc and ¹⁷⁷ Lu.

Results

Our SPECT design can resolve 7.9 mm rods for ^99m Tc (140 keV) and 9.5 mm for ¹⁷⁷ Lu (208 keV) in a hot-rod Derenzo phantom with a 3-min exposure and reach an image contrast of 78% for ^99m Tc and 57% for ¹⁷⁷ Lu using the NEMA IQ phantom with a 6-min exposure. Our modified scatter correction shows an improved contrast-recovery ratio compared to a standard correction.

Conclusions

In this paper, we demonstrate the good performance of our design for whole-body imaging purposes. This adds to our previous demonstration of improved qualitative and quantitative ^99m Tc imaging of brain perfusion and ¹²³ I imaging of dopamine transport with respect to state-of-the-art NaI dual-head cameras. We show that our design provides similar IQ and contrast to the commercial full-ring SPECT VERITON for ^99m Tc. Regarding ¹⁷⁷ Lu imaging of the 208 keV emissions, our design provides similar contrast to that of other state-of-the-art SPECTs with a significant reduction in exposure. The high sensitivity and extended energy range up to 250 keV makes our SPECT design a promising alternative for clinical imaging and theranostics of emerging radionuclides.

Targeted alpha therapy has demonstrated a great efficacy in the treatment of a number of malignancies, but the study of emerging radiopharmaceutical is hindered by the inability of current gamma cameras to image such radiopharmaceuticals in vivo. We use a collimator-less gamma camera consisting of BGO scintillators, multi-channel photomultipliers and an Anger logic circuit to achieve a high sensitivity and obtain planar images of the 225Ac daughters 221Fr and 213Bi for the first time in mice. 0.5 μCi of 225Ac-DOTA-YS5 was injected to a mouse bearing prostate cancer xenografts and imaged 13 days post-injection (0.2 μCi approximated activity). The images reveal the tumor position and the location of other organs with higher uptake. This provides a proof of principle of the power of proximity imaging for 225Ac, and potentially other targeted alpha therapy imaging radionuclides.

Objective.The Office of Radiological Security, U.S. Department of Energy's National Nuclear Security Administration, is implementing a radiological risk reduction program which seeks to minimize or eliminate the use of high activity radiological sources, including¹³⁷Cs, by replacing them with non-radioisotopic technologies, such as x-ray irradiators. The main goal of this paper is to evaluate the equivalence of the dose delivered by gamma- and x-ray irradiators in mice using experimental measurements and Monte Carlo simulations. We also propose a novel biophantom as anin situdose calibration method.Approach.We irradiated mouse carcasses and 3D-printed mouse biophantoms in a¹³⁷Cs irradiator (Mark I-68) and an x-ray irradiator (X-Rad320) at three voltages (160 kVp, 225 kVp and 320 kVp) and measured the delivered radiation dose. A Geant4-based Monte Carlo model was developed and validated to provide a comprehensive picture of gamma- and x-ray irradiation in mice.Main Results.Our Monte Carlo model predicts a uniform dose delivered in soft-tissue for all the explored irradiation programs and in agreement with the absolute dose measurements. Our Monte Carlo model shows an energy-dependent difference between dose in bone and in soft tissue that decreases as photon energy increases. Dose rate depends on irradiator and photon energy. We observed a deviation of the measured dose from the target value of up to -9% for the Mark I-68, and up to 35% for the X-Rad320. The dose measured in the 3D-printed phantoms are equivalent to that in the carcasses within 6% uncertainty.Significance.Our results suggest that 320 kVp irradiation is a good candidate to substitute¹³⁷Cs irradiation barring a few caveats. There is a significant difference between measured and targeted doses for x-ray irradiation that suggests a strong need forin situcalibration, which can be achieved with 3D-printed mouse biophantoms. A dose correction is necessary for bone doses, which can be provided by a Monte Carlo calculation. Finally, the biological implications of the differences in dose rates and dose per photon for the different irradiation methods should be carefully assessed for each small-animal irradiation experiment.

We present a new method to measure sub-microcurie activities of photon-emitting radionuclides in organs and lesions of small animals in vivo. Our technique, named the collimator-less likelihood fit, combines a very high sensitivity collimatorless detector with a Monte Carlo-based likelihood fit in order to estimate the activities in previously segmented regions of interest along with their uncertainties. This is done directly from the photon projections in our collimatorless detector and from the region of interest segmentation provided by an x-ray computed tomography scan. We have extensively validated our approach with 225Ac experimentally in spherical phantoms and mouse phantoms, and also numerically with simulations of a realistic mouse anatomy. Our method yields statistically unbiased results with uncertainties smaller than 20% for activities as low as ~111Bq (3nCi) and for exposures under 30 minutes. We demonstrate that our method yields more robust recovery coefficients when compared to SPECT imaging with a commercial pre-clinical scanner, specially at very low activities. Thus, our technique is complementary to traditional SPECT/CT imaging since it provides a more accurate and precise organ and tumor dosimetry, with a more limited spatial information. Finally, our technique is specially significant in extremely low-activity scenarios when SPECT/CT imaging is simply not viable.