Ultra-Low Count Quantitative SPECT for Alpha-Particle Therapies
用于 α 粒子治疗的超低计数定量 SPECT
基本信息
- 批准号:10446871
- 负责人:
- 金额:$ 52.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-30 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:AccelerationActiniumAddressAlpha Particle EmitterAlpha ParticlesAnatomyAndrogen AntagonistsBiological MarkersBiopsyClinicalClinical TrialsCollaborationsCollimatorComputer ModelsCytotoxic ChemotherapyDCNUDataDaughterDiseaseDoseDose-LimitingEngineeringEvaluationGamma RaysGenerationsGoalsGoldImageIntestinal ContentIntestinesIsotopesJointsLesionMeasuresMethodsModelingModernizationNoiseOrganOutcomePatientsPerformancePhotonsPhysicsPhysiologyProcessProtocols documentationQuality of lifeRadiationRadiation OncologyRadiation ToleranceRadiation therapyRadioisotopesRadiopharmaceuticalsRadiumRegimenResistanceRiskSafetyScanningScheduleSerumSiteSkeletonSystemTechniquesTherapeuticThoriumTimeTreatment ProtocolsWorkadverse event monitoringbasebonecancer cellcastration resistant prostate cancerclinical efficacyclinical imagingclinical translationclinically significantclinically translatabledetectordrug developmentdrug efficacyefficacy evaluationfirst-in-humanimaging approachimaging studyimprovedimproved outcomeindividualized medicineindustry partnerinnovationmennon-invasive imagingnovelparticle therapyradiation absorbed dosereconstructionsimulationsingle photon emission computed tomographytherapy outcometreatment planningtumoruptakevirtual clinical trial
项目摘要
PROJECT SUMMARY:
The overall goal of this project is to develop and comprehensively validate ultra-low count quantitative SPECT
(ULC-QSPECT) methods for alpha particle radiopharmaceutical therapies (αRPTs), including in a first-in-man
trial in patients with bone metastatic castration-resistant prostate cancer. αRPTs, such as those based on
Actinium-225, Thorium-227 and approved Radium-223 isotopes, are an emerging class of cytotoxic therapies
for patients with disseminated metastatic disease using internally administered alpha-particle emitting agents.
Despite the great potential of these therapies, current αRPT regimens are not personalized, with administered
activity dependent merely on mass, likely leading to non-optimal therapy. To address this challenge, there is a
crucial unmet need for methods to measure the isotope uptake, and hence the absorbed radiation dose with
these therapies, both at sites of disease and in vital dose-limiting organs. SPECT provides a clinically translatable
mechanism to achieve this goal. However, a key challenge to SPECT-based quantification is that the
administered activities in αRPTs are orders of magnitude lower than a typical SPECT scan, leading to ultra-low
detected count levels. Conventional approaches to quantification that reconstruct the isotope distribution and
estimate the regional uptake from reconstructed images are erroneous at these low count levels. To address
this issue, we put forwards a novel computational ULC-QSPECT framework for regional activity estimation from
αRPTs. These methods quantify regional uptake directly from projection data skipping the reconstruction step,
and at the same time, extract the maximal possible information from the acquired projection data. For this
purpose, we propose novel methods that accurately model the physics of imaging αRPTs, including stray-
radiation-related noise, use data from multiple-energy windows, incorporate scatter-window photons for
quantification, and process data in list-mode format. Our extensive preliminary data show that the proposed
methods result in nearly unbiased uptake and variances close to the theoretical limit. We propose to further
develop and rigorously evaluate these methods. Our proposed evaluations include studies over multiple
scanners with different detectors and different collimator configurations. Further, our goal is clinical translation
of these methods. Towards this goal, we propose to clinically evaluate these methods for measuring activity
concentrations at sites of uptake of [223Ra]RaCl2 in men with castrate resistant prostate cancer. These methods
will enable quantification of activity at disease sites in the skeleton as well as clearance through the intestine.
The approach has direct relevance to patients as it achieves noninvasive imaging of low-administered activity
therapies. Further, this proposal has substantial potential impact to improve both safety and efficacy of drug
development efforts in this rapidly evolving space. Further, the methods developed in this proposal will
strengthen the clinical utility of SPECT in managing patients with these therapies.
项目总结:
该项目的总体目标是开发和全面验证超低计数定量SPECT
阿尔法粒子放射药物治疗(αRPTS)的方法,包括首例人
在骨转移耐去势前列腺癌患者中的试验。αRPT,例如基于
~(225)Ac、~(227)Th~(227)和经批准的~(223)Re同位素是一种新兴的细胞毒性疗法
用于使用内部注射的阿尔法粒子发射剂的播散性转移性疾病患者。
尽管这些疗法具有巨大的潜力,但目前的αRPT方案并不是个性化的,
活动仅依赖于质量,很可能导致非最佳治疗。为了应对这一挑战,有一个
对测量同位素摄取量的方法的关键需求未得到满足,因此
这些疗法既适用于疾病部位,也适用于重要的剂量限制器官。SPECT提供了一种临床可翻译的
实现这一目标的机制。然而,基于SPECT的量化的一个关键挑战是
αRPT中的管理活动比典型的SPECT扫描低一个数量级,导致超低
检测到计数级别。重建同位素分布的传统量化方法和
在这些低计数水平下,从重建图像估计区域摄取是错误的。致信地址
针对这一问题,我们提出了一个新的用于区域活动估计的计算ULC-QSPECT框架
α报告。这些方法直接从跳过重建步骤的投影数据量化区域摄取,
同时,从获取的投影数据中提取最大可能信息。为了这个
目的:我们提出了精确模拟成像αRPT的物理模型的新方法,其中包括杂散模型。
与辐射相关噪声,使用来自多个能量窗的数据,结合散射窗光子
量化,并以列表模式格式处理数据。我们广泛的初步数据显示,拟议中的
方法的结果是近乎无偏见的吸收和接近理论极限的方差。我们建议进一步
开发并严格评估这些方法。我们建议的评估包括多项研究
具有不同探测器和不同准直器配置的扫描仪。此外,我们的目标是临床翻译
这些方法中的一个。为了达到这个目标,我们建议对这些测量活动性的方法进行临床评估。
去势抵抗前列腺癌患者摄取[223Ra]RaCl2部位的浓度。这些方法
将能够量化骨骼中疾病部位的活动以及通过肠道的清除。
该方法与患者直接相关,因为它实现了对低剂量活动的非侵入性成像
治疗。此外,这项建议对提高药物的安全性和有效性具有重大的潜在影响。
在这一快速发展的空间中的发展努力。此外,本提案中制定的方法将
加强SPECT在治疗患者中的临床应用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Abhinav K Jha其他文献
Abhinav K Jha的其他文献
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{{ truncateString('Abhinav K Jha', 18)}}的其他基金
Ultra-Low Count Quantitative SPECT for Alpha-Particle Therapies
用于 α 粒子治疗的超低计数定量 SPECT
- 批准号:
10704042 - 财政年份:2022
- 资助金额:
$ 52.62万 - 项目类别:
A no-gold-standard framework to objectively evaluate quantitative imaging methods with patient data
利用患者数据客观评估定量成像方法的非金标准框架
- 批准号:
10375582 - 财政年份:2021
- 资助金额:
$ 52.62万 - 项目类别:
A no-gold-standard framework to objectively evaluate quantitative imaging methods with patient data
利用患者数据客观评估定量成像方法的非金标准框架
- 批准号:
10553677 - 财政年份:2021
- 资助金额:
$ 52.62万 - 项目类别:
A framework to quantify and incorporate uncertainty for ethical application of AI-based quantitative imaging in clinical decision making
量化和纳入基于人工智能的定量成像在临床决策中的伦理应用的不确定性的框架
- 批准号:
10599754 - 财政年份:2021
- 资助金额:
$ 52.62万 - 项目类别:
A no-gold-standard framework to objectively evaluate quantitative imaging methods with patient data
利用患者数据客观评估定量成像方法的非金标准框架
- 批准号:
10185997 - 财政年份:2021
- 资助金额:
$ 52.62万 - 项目类别:
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