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

以放射性核素为基础的治疗，结合有针对性的诊断和治疗放射性药物来精确治疗癌症，已经彻底改变了核医学领域。尽管其增长迅速，但治疗应用仍处于起步阶段，并将受益于放射性核素摄取的准确定量和放射性核素治疗后剂量测定。目前，通常只进行相对量化，这在定义具有代表性的基于图像的度量方面存在许多限制。准确了解不同器官的活性浓度，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化和它们在临床中的安全个性化实施。然而，使用先进的SPECT/CT系统进行绝对定量，可以通过准确地结合系统物理特性和成像物理特性，准确地测量体内生物分布中的放射性药物浓度。虽然最初只能对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，如镥-177 （177Lu）、铟-111 （111In）、锕-225 （225Ac）和碘-123 （123I）。这些同位素最近作为治疗剂受到了相当大的关注，无论是在KCL内部，许多这样的放射性标记剂被开发和探索用于治疗应用，还是在其他领域。SPECT/CT的绝对定量可能有助于评估肿瘤的疾病负担和治疗反应（预测治疗效果和多种治疗的需求）。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的施用，以实现最高的肿瘤递送剂量，同时限制潜在的毒性（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至关重要。准确了解一种新的治疗药物的剂量学特征可以加速其在该领域的转化，正如最近68Ga-/177Lu-PSMA对前列腺癌临床治疗的影响所显示的那样，该领域具有快速增长的潜力。在这个博士项目中，最先进的临床前SPECT/CT多针孔准直成像仪的成像能力和性能将被研究用于使用放射性同位素如131I， 188Re, 212Pb， 225Ac等的治疗应用。将通过使用GATE蒙特卡罗模拟的基于精确体素的剂量学，探索使用具有挑战性的放射性同位素进行绝对定量的进一步改进。具体目标将集中在：-使用具有治疗学同位素的创新高能多针孔准直器对纳米扫描SPECT/CT进行性能评估-识别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，获取和重建方案-开发基于体素的剂量学，例如通过蒙特卡罗模拟；使用定量临床前SPECT/CT图像并可能与器官定义的剂量学方法进行比较-探索时间序列的数据减少方法，以简化数据收集并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.