Title of project: Evaluation of the quantitative accuracy and radiation dosimetry of an advanced pre-clinical multipinhole SPECT/CT theranostic imag

基于放射性核素的治疗疗法，将靶向诊断和治疗放射性药物结合起来，用于癌症的精确治疗，已经彻底改变了核医学领域。尽管增长迅速，但鼻咽术的应用仍处于初级阶段，将受益于放射性核素摄取的准确量化和放射性核素治疗后的剂量测定。目前，只有相对量化是常规执行的，这在定义基于图像的代表性指标方面存在许多限制。准确了解不同器官的放射性浓度，从而了解吸收辐射剂量的区域分布(剂量学)将有助于治疗药物的转换及其安全的个性化实施进入临床。然而，使用先进的SPECT/CT系统的绝对定量可以通过准确地结合系统物理特性和成像物理来精确测量体内生物分布中的放射性药物浓度。虽然最初只可能对99mTc标记的放射性药物进行绝对定量，但现在已经扩展到其他同位素，如Lu177(177Lu)、In111(111In)、Ac-225(225Ac)和I-123(123I)。这些同位素最近在KCL内部作为治疗试剂受到了相当大的关注，那里开发和探索了许多这样的放射性标记试剂用于治疗和其他方面的应用。SPECT/CT的绝对定量可以潜在地帮助评估肿瘤的疾病负担和治疗反应(预测治疗效果和需要多种治疗)。此外，定量SPECT/CT的关键目标之一是改进对关键器官的剂量估计，以优化放射性核素治疗剂量给药，以获得最高的肿瘤递送剂量，同时限制潜在毒性(对关键器官的剂量)。为了解释放射生物学剂量-反应关系并将结果转化为临床应用，准确的剂量测定在临床前治疗学中是至关重要的。准确了解一种新的治疗试剂的剂量分布可以加速其向一个领域的转化，正如最近68Ga-/177Lu-PSMA应用于前列腺癌临床治疗所表明的那样，这个领域具有快速增长的潜力。在这个PHD项目中，将研究最先进的临床前SPECT/CT多针孔准直仪成像器的成像能力和性能，以用于治疗应用，使用放射性同位素，如131I，188Re，212Pb，225Ac等。将通过使用基于精确体素的蒙特卡罗模拟来探索在使用放射性同位素进行绝对定量成像方面的进一步改进。具体目标将侧重于以下方面：-使用具有热声学同位素的创新高能多针孔准直器对NanScan SPECT/CT进行性能评估-确定影响定量准确性的因素-分析和改进SPECT成像链，包括校准、校正、获取和重建计划-开发基于体素的剂量测定，例如通过蒙特卡罗模拟，使用临床前的定量SPECT/CT图像和可能与器官定义的剂量测定方法进行比较；探索时间序列的数据减少方法，以简化数据收集和减少提供放射性药物停留时间所需的时间点数量。

Radionuclide-based theranostics, where targeted diagnostic and therapeutic radiopharmaceuticals are combined for the precision treatment of cancer, has revolutionised the field of nuclear medicine. Despite its rapid growth, theranostic applications are in their infancy and will benefit from accurate quantification of radionuclide uptake and post radionuclide therapy dosimetry. Currently, only relative quantification is routinely performed, which comes with numerous limitations in defining representative image-based metrics. Accurate knowledge of activity concentrations across different organs and consequently, the regional distribution of absorbed radiation dose (dosimetry) would aid both translation of theranostic agents and their safe personalised implementation into the clinic. Absolute quantification using advanced SPECT/CT systems, however, can accurately measure radiopharmaceutical concentrations across an in vivo biodistribution by accurately incorporating the system physical characteristics and the imaging physics. Whilst initially only possible for 99mTc-labelled radiopharmaceuticals, absolute quantification has now expanded to other isotopes such as Lutetium-177 (177Lu), Indium-111 (111In), Actinium-225 (225Ac) and Iodine-123 (123I).These isotopes have recently received considerable attention as theranostic agents, both within KCL, where a number of such radio-labelled agents are developed and explored for theranostic applications, and beyond. Absolute quantification with SPECT/CT could potentially aid assessment of disease burden and therapy response in tumours (prediction of therapeutic efficacy and requirement for multiple therapies). In addition, one of the key objectives of quantitative SPECT/CT is to improve dose estimations to critical organs to optimize radionuclide therapy dose administration to achieve the highest delivered tumour dose while limiting potential toxicity (dose to critical organs). Accurate dosimetry is critical in preclinical theranostics in order to interpret radiobiological dose-response relationships and to translate results into clinical applications. Accurate knowledge of the dosimetric profile of a new theranostic agent can accelerate its transltion into a field that, as shown recently by the impact of 68Ga-/177Lu-PSMA into clinical treatment of prostate cancer, has potential for rapid growth.In this PhD project, the imaging capability and performance of a state-of-the-art preclinical SPECT/CT multipinhole collimator imager will be investigated for theranostic applications using radioisotopes such as 131I, 188Re, 212Pb, 225Ac, etc. Further improvements in absolute quantification using radioisotopes that are challenging to image will be explored through the use of precise voxel-based dosimetry with GATE Monte Carlo simulation. Specific goals will focus on:- performance evaluation of nanoScan SPECT/CT using innovative high-energy multipinhole collimators with theranostics isotopes- identifying factors that compromise quantitative accuracy- analysing and improving the SPECT imaging chain, including calibrations, corrections, acquisition, and reconstruction schemes- developing voxel-based dosimetry, for example through Monte Carlo simulation, using quantitative preclinical SPECT/CT images and possible comparison to organ-defined dosimetry approaches- exploring data reduction methodologies to time sequences in order to simplify data collection and reduce the number of time points required to provide radiopharmaceutical residence times.