A Projection-Domain Low-Count Quantitative SPECT Method for α-Particle-Emitting Radiopharmaceutical Therapy.

Single-photon emission-computed tomography (SPECT) provides a mechanism to estimate regional isotope uptake in lesions and at-risk organs after administration of α-particle-emitting radiopharmaceutical therapies (α-RPTs). However, this estimation task is challenging due to the complex emission spectra, the very low number of detected counts (~20 times lower than in conventional SPECT), the impact of stray-radiation-related noise at these low counts, and the multiple image-degrading processes in SPECT. The conventional reconstruction-based quantification methods are observed to be erroneous for α-RPT SPECT. To address these challenges, we developed a low-count quantitative SPECT (LC-QSPECT) method that directly estimates the regional activity uptake from the projection data (obviating the reconstruction step), compensates for stray-radiation-related noise, and accounts for the radioisotope and SPECT physics, including the isotope spectra, scatter, attenuation, and collimator-detector response, using a Monte Carlo-based approach. The method was validated in the context of 3-D SPECT with 223Ra, a commonly used radionuclide for α-RPT. Validation was performed using both realistic simulation studies, including a virtual clinical trial, and synthetic and 3-D-printed anthropomorphic physical-phantom studies. Across all studies, the LC-QSPECT method yielded reliable regional-uptake estimates and outperformed the conventional ordered subset expectation-maximization (OSEM)-based reconstruction and geometric transfer matrix (GTM)-based post-reconstruction partial-volume compensation methods. Furthermore, the method yielded reliable uptake across different lesion sizes, contrasts, and different levels of intralesion heterogeneity. Additionally, the variance of the estimated uptake approached the Cramér-Rao bound-defined theoretical limit. In conclusion, the proposed LC-QSPECT method demonstrated the ability to perform reliable quantification for α-RPT SPECT.

Practical considerations for quantitative clinical SPECT/CT imaging of alpha particle emitting radioisotopes.

Rationale: Alpha particle emitting radiopharmaceuticals are generating considerable interest for the treatment of disseminated metastatic disease. Molecular imaging of the distribution of these agents is critical to safely and effectively maximize the clinical potential of this emerging drug class. The present studies aim to investigate the feasibility and limitations of quantitative SPECT for 223Ra, 225Ac and 227Th. Methods: Three state-of-the-art SPECT/CT systems were investigated: the GE Discovery NM/CT 670, the GE Optima NM/CT 640, and the Siemens Symbia T6. A series of phantoms, including the NEMA IEC Body phantom, were used to compare and calibrate each camera. Additionally, anthropomorphic physical tumor and vertebrae phantoms were developed and imaged to evaluate the quantitative imaging protocol. Results: This work describes and validates a methodology to calibrate each clinical system. The efficiency of each gamma camera was analyzed and compared. Using the calibration factors obtained with the NEMA phantom, we were able to quantify the activity in 3D-printed tissue phantoms with an error of 2.1%, 3.5% and 11.8% for 223Ra, 225Ac, and 227Th, respectively. Conclusion: The present study validates that quantitative SPECT/CT imaging of 223Ra, 225Ac, and 227Th is achievable but that careful considerations for camera configuration are required. These results will aid in future implementation of SPECT-based patient studies and will help to identify the limiting factors for accurate image-based quantification with alpha particle emitting radionuclides.

Effect of barium-coated halloysite nanotube addition on the cytocompatibility, mechanical and contrast properties of poly(methyl methacrylate) cement.

Halloysite nanotubes (HNTs) were investigated as a platform for tunable nanoparticle composition and enhanced opacity in poly(methyl methacrylate) (PMMA) bone cement. Halloysite has been widely used to increase the mechanical properties of various polymer matrices, in stark contrast to other fillers such as barium sulfate that provide opacity but also decrease mechanical strength. The present work describes a dry deposition method for successively fabricating barium sulfate nanoparticles onto the exterior surface of HNTs. A sintering process was used to coat the HNTs in barium sulfate. Barium sulfate-coated HNTs were then added to PMMA bone cement and the samples were tested for mechanical strength and tailored opacity correlated with the fabrication ratio and the amount of barium sulfate-coated HNTs added. The potential cytotoxic effect of barium-coated HNTs in PMMA cement was also tested on osteosarcoma cells. Barium-coated HNTs were found to be completely cytocompatible, and cell proliferation was not inhibited after exposure to the barium-coated HNTs embedded in PMMA cement. We demonstrate a simple method for the creation of barium-coated nanoparticles that imparted improved contrast and material properties to native PMMA. An easy and efficient method for coating clay nanotubes offers the potential for enhanced imaging by radiologists or orthopedic surgeons.