1st Supervisor: Dr Lefteris Livieratos, King’s College London
2nd Supervisor: Prof Andrew Reader, King’s College London
Aims of the Project:
The project aims to utilise PET and SPECT imaging in order to improve the spatial resolution and noise properties of SPECT by guiding SPECT image reconstruction by the higher spatial resolution PET images in a theragnostics setting e.g. 68Ga-DOTATATE and 177Lu-DOTATATE in prostate cancer. Subsequently the project aims to improve accuracy of image-based dosimetry.
Lay Summary:
Single Photon Emission Computed Tomography (SPECT) is commonly used to verify the location of radionuclides used to treat tumours in molecular radiotherapy (MRT) and in order to estimate the radiation dose delivered to target tumours and normal organs during therapy. Many radionuclides used in MRT, along with particle radiation capable of delivering localised high levels of radiation dose, also emit low-dose radiation which isn’t absorbed within the body, hence is suitable for imaging. As an example, 177Lu-DOTATATE has been used over the past few years for the treatment of neuro-endocrine tumours; Following initial PET imaging assessment with a suitable tumour-seeking radiopharmaceutical 68Ga-DOTATATE, a typical therapy cycle involves verification SPECT imaging after administration of 177Lu-DOTATATE. Recently, the introduction of 177Lu-PSMA in clinical use for metastatic castrate-resistant prostate cancer has shown promising outcomes; Following a multi-centre clinical trial and the recent FDA approval of the theragnostic pair 68Ga-PSMA/177Lu-PSMA, this is a clinical area of potentially high impact due to the prevalence of this type of cancer in patient population.
However, SPECT is limited by relatively poor sharpness which impacts the accuracy of defining the radionuclide concentration in the body and subsequently the radiation dose delivered. This is potentially a major limitation for personalisation of radionuclide therapies, where the dose can be tailored to the individual patient based on the accompanying SPECT data of each therapy cycle, instead of an one-dose-fits-all approach. The use of the pre-therapy PET, a modality with typically a two-fold improved sharpness over SPECT, can potentially be used to improve subsequent SPECT imaging as part of a synergistic approach. The aim is to utilise both imaging modalities in order to improve the sharpness and noise properties of SPECT by guiding SPECT image reconstruction by the higher sharpness PET. This approach has recently been introduced in a generalised context of radionuclide thearpies, however, a number of questions still remain unaddressed before clinical implementation could be considered with a specific clinical application in mind. This novel approach makes use of a mathematical algorithm to guide the formation of SPECT images (poorer sharpness) by the PET images (improved sharpness) as the two sets of radiopharmaceuticals should have the same distribution in the body. Improvements in terms of sharpness and reduced noise can be translated to improved estimation of radionuclide concentration and ultimately, improved estimation of radiation dose delivered in the body which is the pinnacle for personalised therapy planning.