Advanced planar image reconstruction for targeted alpha therapy

用于靶向 α 治疗的高级平面图像重建

• 批准号: 10453023
• 负责人: Charles Ross Schmidtlein
• 金额: $ 24.18万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453023
• 关键词: Address; Alpha Particles; Biodistribution; Caliber; Cell Cycle; Cells; Clinical; DNA Double Strand Break; Data; Development; Distributional Activity; Dose; Dose-Rate; Environment; FOLH1 gene; Fractionation; Generations; Glioma; Goals; Image; Knowledge; Linear Energy Transfer; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measures; Mediating; Metastatic Prostate Cancer; Metastatic to; Methods; Mission; Modeling; Neuroendocrine Tumors; Noise; Normal tissue morphology; Organ; Outcome; Patient-Focused Outcomes; Patients; Performance; Public Health; Radiation Dose Unit; Radioisotopes; Radiopharmaceuticals; Research; Schedule; Surrogate Markers; System; Testing; Tissues; Toxic effect; United States National Institutes of Health; X-Ray Computed Tomography; base; cancer cell; castration resistant prostate cancer; cell killing; cytotoxicity; design; digital; dosimetry; image reconstruction; imaging modality; improved; leukemia; low dose computed tomography; melanoma; novel; personalized medicine; personalized predictions; physical model; prevent; quantitative imaging; reconstruction; response; single photon emission computed tomography; standard of care; success; targeted treatment; therapy design; tumor

Project Summary Title: Advanced Planar Image Reconstruction for Targeted Alpha Therapy Targeted Alpha Therapy (TAT) based on the alpha-emitting radiopharmaceuticals (AER) has been recently successfully applied as a treatment for many advanced-stage cancers incurable with conventional methods. However, current methods of imaging the biodistribution of AER are sub-optimal, due to very low administered activity. As a result, AER biodistributions are unknown and hence, absorbed dose distributions for AER are unknown. Thus, our ability to anticipate normal tissue toxicity and prescribe personalized treatment is compromised. Accurate quantitative imaging of the AER biodistribution is necessary to remedy this situation. To address this need, our project’s long-term goal is development of a method for the generation of accurate projection images of AER (proj-AER) using low-count AER planar data and co-registered low-dose CT images acquired on SPECT/CT cameras. The obtained proj-AER combined with CT will permit accurate AER activity estimation that will be used as input data for a dosimetry model, which will provide information on the radiation dose to organs/tumor. The objective of this proposal is to develop a novel sparsity promoting reconstruction method based on a physical model for planar AER imaging and perform a proof-of-concept study of its superior quantitative accuracy vs. standard-of-care (SOC). We will use low-count 225Ac planar images and co-registered low-dose CT images acquired on SPECT/CT cameras. Physical and digital phantoms will be employed. Guided by strong preliminary data, this objective will be attained by pursuing two specific aims: 1) Develop and validate an accurate projected planar activity distribution reconstruction method for AER; and 2) Compare performance of our method with current SOC in 225Ac quantitation tasks using simulated and physical-phantom planar/CT data acquired on SPECT/CT camera. The approach will rely on a physical imaging model containing the system kernels and regularization. To control noise, we will use sparsity promoting regularization with envelope of the l0-norm. The fixed-point proximity-operator approach will be used to solve the resulting nonconvex minimization problem. The effects of noise on organ/tumor activity estimates will be accounted for with an ensemble mean squared error performance metric. The estimation tradeoffs of bias and variance will be explored. Simulated dosimetry tasks will be used to demonstrate performance improvements. Outcomes: We will establish that the novel planar reconstruction method is ready for testing in the clinical environment. The measure of success is defined as substantial (>50%) improvement in precision and accuracy in the estimation of regional activity concentration of AER. The proposed research is significant because it is expected that the direct quantitative imaging of AER will allow optimized personalized design of TAT including activity/fractionation schedule. It will also enable rational assessment of the utility of imaging AER surrogates. Ultimately, such knowledge will lead to higher likelihood of response and cure for patients with advanced stages of many cancers.

项目总结