Alpha-emitter Imaging for Dosimetry and Treatment Planning
用于剂量测定和治疗计划的阿尔法发射体成像
基本信息
- 批准号:10713710
- 负责人:
- 金额:$ 45.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-19 至 2028-08-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAddressAdoptedAlpha Particle EmitterAlpha ParticlesAreaBiological Response Modifier TherapyCharacteristicsClinicalClinical TrialsCollaborationsComplexDataData CollectionDaughterDevelopmentDiagnostic ImagingDiagnostic ProcedureDiscipline of Nuclear MedicineDisseminated Malignant NeoplasmDistributional ActivityDoseDrug KineticsGamma RaysGoalsHistologicImageKnowledgeLinear Energy TransferMaximum Tolerated DoseMeasuresMethodologyMethodsModalityModelingMonitorOrganOutcomePET/CT scanPatient SelectionPatient-Focused OutcomesPatientsPhasePhotonsPhysicsProceduresProgram Research Project GrantsPropertyProtocols documentationRadiobiologyRadioisotopesRadiopharmaceuticalsResistanceSurfaceSystemTechniquesTestingTimeTissuesToxic effectTreatment EfficacyTreatment ProtocolsUncertaintyValidationWorkX-Ray Computed Tomographyabsorptionanimal dataanimal-assisted therapycancer cellcancer therapychemotherapyclinical practicecostdesigndosimetryimage reconstructionimaging modalityimprovedimproved outcomein vivoindividualized medicinememberoptical spectrapatient populationpatient responsepatient screeningquantitative imagingreconstructionresponsescreeningsingle photon emission computed tomographytherapy outcometreatment optimizationtreatment planningtumor
项目摘要
Radiopharmaceutical therapy with α-particle emitters (αRPT) is a highly effective cancer therapy modality; it
delivers potent alpha-particle radiation to cancer cells and is therefore not susceptible to resistance seen with
most other cancer therapies. It is also unique in that alpha-emitters also emit photons that can be imaged by
nuclear medicine modalities. This allows for patient-specific treatment planning and optimization of patient
therapy. These unique features of αRPT have not been used, however, because αRPT is so effective that the
activity used to treat patient is too low to be imaged with conventional nuclear medicine imaging methods. In this
project we will develop and implement accurate single photon emission computed tomography (SPECT) imaging
methods that overcome this limitation. Our hypothesis is that enabling quantitative αRPT imaging and making it
convenient so that it is widely adopted will improve the outcome of patients treated with αRPT. The distribution
of the radionuclide in vivo is a prerequisite for estimating the absorbed dose distributions needed to plan and
optimize αRPT’s. There are several significant challenges to imaging the distribution of α-emitters in patients.
Due to their high linear energy transfer (LET) and resulting lethality, low administered activities are used. Typical
decay chains include multiple daughter radionuclides that emit photons, and it is important to also determine
their activity distribution. Also, the photon emission spectrum for α-emitters typically has many low-abundance
gamma rays spread over a wide energy range. These properties have made imaging-based dosimetry difficult;
the imaging that has been performed has not been quantitatively rigorous. We propose to develop imaging
reconstruction methods applicable to clinical SPECT systems that will account for the complex imaging physics
and allow for validated quantitative SPECT imaging of αRPT for accurate dosimetry calculations. The overall
goal is to incorporate such quantitative SPECT imaging into a clinically implementable imaging workflow that can
provide accurate dosimetry for treatment planning and efficacy monitoring. Our group, in collaboration with
members of a Hopkins startup company, Radiopharmaceutical Imaging and Dosimetry, LLC (Rapid), have
already made considerable progress on SPECT imaging of αRPT agents. In Aim1, we will extend this work to
develop quantitative reconstruction methods for SPECT imaging of alpha emitters that produce accurate
measures of activity distribution for dosimetry which will also be useful for SPECT diagnostic imaging in general.
Another challenge for imaging αRPT is the requirement that patients return for several imaging sessions to obtain
the needed pharmacokinetics in normal organs and tumors. Thus, in Aim 2 we will investigate the trade-off
between number of imaging time-points and the accuracy of dosimetry. In Aim 3 we will apply the developed
imaging method and statistically analyze the relationships between quantitative image measures, dosimetry,
dose-response, and therapy outcome. In Aim 4, we consider several potential surrogate radionuclides and
assess their utility for pre-therapy dosimetry.
使用α粒子发射体的放射性药物治疗(αRPT)是一种高效的癌症治疗方式,
向癌细胞提供有效的α粒子辐射,因此不易产生耐药性,
大多数其他癌症治疗方法。它的独特之处还在于α发射体也发射光子,这些光子可以通过
核医学模式。这允许患者特定的治疗计划和患者的优化。
疗法然而,αRPT的这些独特功能尚未被使用,因为αRPT非常有效,
用于治疗患者的放射性太低而不能用常规核医学成像方法成像。在这
项目我们将开发和实施准确的单光子发射计算机断层扫描(SPECT)成像
克服这种限制的方法。我们的假设是,使定量αRPT成像并使其
方便,使其被广泛采用将改善αRPT治疗患者的结局。分布
放射性核素在体内的剂量分布是估算计划所需吸收剂量分布的先决条件,
优化αRPT。对患者体内α发射体的分布进行成像存在几个重大挑战。
由于它们的高线性能量转移(LET)和导致的致死性,使用低施用活性。典型
衰变链包括发射光子的多个子放射性核素,确定这一点也很重要
其活动分布。此外,α-发射体的光子发射光谱通常具有许多低丰度
伽马射线的能量范围很广这些特性使得基于成像的剂量测定变得困难;
已经进行的成像在数量上并不严格。我们建议发展成像技术
适用于临床SPECT系统的重建方法,将考虑复杂的成像物理学
并允许对αRPT进行经验证的定量SPECT成像,以进行准确的剂量测定计算。整体
目标是将这种定量SPECT成像结合到临床可实施的成像工作流程中,
为治疗计划和疗效监测提供准确的剂量测定。我们的团队与
霍普金斯的一家初创公司--放射性药物成像和剂量测定有限责任公司(Rapid)的成员,
已经在αRPT剂的SPECT成像方面取得了相当大的进展。在Aim 1中,我们将把这项工作扩展到
开发用于α发射体SPECT成像的定量重建方法,
用于剂量测定的放射性分布的测量,其通常也将用于SPECT诊断成像。
αRPT成像的另一个挑战是要求患者返回进行多次成像,以获得
正常器官和肿瘤中所需的药代动力学。因此,在目标2中,我们将研究权衡
成像时间点的数量和剂量测定的准确性之间的关系。在目标3中,我们将应用开发的
成像方法,并统计分析定量图像测量,剂量学,
剂量反应和治疗结果。在目标4中,我们考虑了几种潜在的替代放射性核素,
评估其用于治疗前剂量测定的效用。
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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Yong Du其他文献
Yong Du的其他文献
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{{ truncateString('Yong Du', 18)}}的其他基金
High Energy and Spatial Resolution Multi-Isotope SPECT Imaging of Targeted Alpha-Emitters and their Daughters
目标α发射体及其子体的高能量和空间分辨率多同位素 SPECT 成像
- 批准号:
10275637 - 财政年份:2021
- 资助金额:
$ 45.04万 - 项目类别:
High Energy and Spatial Resolution Multi-Isotope SPECT Imaging of Targeted Alpha-Emitters and their Daughters
目标α发射体及其子体的高能量和空间分辨率多同位素 SPECT 成像
- 批准号:
10470322 - 财政年份:2021
- 资助金额:
$ 45.04万 - 项目类别:
Hyperspectral Single Photon Imaging of Targeted Alpha-Emitters
目标阿尔法发射器的高光谱单光子成像
- 批准号:
10436389 - 财政年份:2021
- 资助金额:
$ 45.04万 - 项目类别:
Hyperspectral Single Photon Imaging of Targeted Alpha-Emitters
目标阿尔法发射器的高光谱单光子成像
- 批准号:
10633193 - 财政年份:2021
- 资助金额:
$ 45.04万 - 项目类别:
High Energy and Spatial Resolution Multi-Isotope SPECT Imaging of Targeted Alpha-Emitters and their Daughters
目标α发射体及其子体的高能量和空间分辨率多同位素 SPECT 成像
- 批准号:
10703387 - 财政年份:2021
- 资助金额:
$ 45.04万 - 项目类别:
Hyperspectral Single Photon Imaging of Targeted Alpha-Emitters
目标阿尔法发射器的高光谱单光子成像
- 批准号:
10311159 - 财政年份:2021
- 资助金额:
$ 45.04万 - 项目类别:
Multi-Modality Quantitative Imaging for Evaluation of Response to Cancer Therapy
用于评估癌症治疗反应的多模态定量成像
- 批准号:
10437852 - 财政年份:2011
- 资助金额:
$ 45.04万 - 项目类别:
Multi-Modality Quantitative Imaging for Evaluation of Response to Cancer Therapy
用于评估癌症治疗反应的多模态定量成像
- 批准号:
10208790 - 财政年份:2011
- 资助金额:
$ 45.04万 - 项目类别:
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