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

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.