RESUMO
PURPOSE: Despite a rise in clinical use of radiopharmaceutical therapies, the biological effects of radionuclides and their relationship with absorbed radiation dose are poorly understood. Here, we set out to define this relationship for Auger electron emitters [99mTc]TcO4- and [123I]I- and ß--particle emitter [188Re]ReO4-. Studies were carried out using genetically modified cells that permitted direct radionuclide comparisons. METHODS AND MATERIALS: Triple-negative MDA-MB-231 breast cancer cells expressing the human sodium iodide symporter (hNIS) and green fluorescent protein (GFP; MDA-MB-231.hNIS-GFP) were used. In vitro radiotoxicity of [99mTc]TcO4-, [123I]I-, and [188Re]ReO4- was determined using clonogenic assays. Radionuclide uptake, efflux, and subcellular location were used to calculate nuclear absorbed doses using the Medical Internal Radiation Dose (MIRD) formalism. In vivo studies were performed using female NSG mice bearing orthotopic MDA-MB-231.hNIS-GFP tumors and compared with X-ray-treated (12.6-15 Gy) and untreated cohorts. Absorbed dose per unit activity in tumors and sodium iodide symporter-expressing organs was extrapolated to reference human adult models using OLINDA/EXM. RESULTS: [99mTc]TcO4- and [123I]I- reduced the survival fraction only in hNIS-expressing cells, whereas [188Re]ReO4- reduced survival fraction in hNIS-expressing and parental cells. [123I]I- required 2.4- and 1.5-fold lower decays/cell to achieve 37% survival compared with [99mTc]TcO4- and [188Re]ReO4-, respectively, after 72 hours of incubation. Additionally, [99mTc]TcO4-, [123I]I-, and [188Re]ReO4- had superior cell killing effectiveness in vitro compared with X-rays. In vivo, X-ray led to a greater median survival compared with [188Re]ReO4- and [123I]I- (54 days vs 45 and 43 days, respectively). Unlike the X-ray cohort, no metastases were visualized in the radionuclide-treated cohorts. Extrapolated human absorbed doses of [188Re]ReO4- to a 1 g tumor were 13.8- and 11.2-fold greater than for [123I]I- in female and male models, respectively. CONCLUSIONS: This work reports reference dose-effect data using cell and tumor models for [99mTc]TcO4-, [123I]I-, and [188Re]ReO4- for the first time. We further demonstrate the tumor-controlling effects of [123I]I- and [188Re]ReO4- in comparison with external beam radiation therapy.
RESUMO
Positron emission particle tracking (PEPT) enables 3D localization and tracking of single positron-emitting radiolabelled particles with high spatiotemporal resolution. The translation of PEPT to the biomedical imaging field has been limited due to the lack of methods to radiolabel biocompatible particles with sufficient specific activity and protocols to isolate a single particle in the sub-micrometre size range, below the threshold for capillary embolization. Here we report two key developments: the synthesis and 68Ga-radiolabelling of homogeneous silica particles of 950 nm diameter with unprecedented specific activities (2.1 ± 1.4 kBq per particle), and the isolation and manipulation of a single particle. We have combined these developments to perform in vivo PEPT and dynamic positron emission tomography (PET) imaging of a single radiolabelled sub-micrometre size particle using a pre-clinical positron emission tomography/computed tomography scanner. This work opens possibilities for quantitative assessment of haemodynamics in vivo in real time, at the whole-body level using minimal amounts of injected radioactive dose and material.
Assuntos
Tomografia por Emissão de Pósitrons , Animais , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos de Gálio/química , Camundongos , Dióxido de Silício/química , Tamanho da Partícula , Nanopartículas/química , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodosRESUMO
Resolution recovery (RR) techniques in positron emission tomography (PET) imaging aim to mitigate spatial resolution losses and related inaccuracies in quantification by using a model of the system's point spread function (PSF) during reconstruction or post-processing. However, including PSF modeling in fully 3-D image reconstruction is far from trivial as access to the scanner-specific forward and back-projectors is required, along with access to the 3-D sinogram data. Hence, post-reconstruction RR methods, such as the Richardson-Lucy (RL) algorithm, can be more practical. However, the RL method leads to relatively rapid noise amplification in early image iterations, giving inferior image quality compared to iterates obtained by placing the PSF model in the reconstruction algorithm. We propose a post-reconstruction RR method by synthesizing PET data by a forward projection of an initial real data reconstruction (such reconstructions are usually available via a scanner's standard reconstruction software). The synthetic PET data are then used to reconstruct an image, but crucially now including a modeled PSF within the system model used during reconstruction. Results from simulations and real data demonstrate the proposed method improves image quality compared to the RL algorithm, whilst avoiding the need for scanner-specific projectors and raw sinogram data (as required by standard PSF modeling within reconstruction).