Innovative Kinetic Modelling Strategies for Radiometabolite Analysis using Total-Body PET and Simultaneous PET-MR Imaging

The classical method of PET quantification using kinetic modelling requires invasive blood sampling as previously described. The radiometabolite experiments require blood and tis- sue samples from 6-15 animals and need repeating for each new tracer developed. A recent method has been developed to extract the radiotracer blood curve from PET scans which

does not require blood sampling [112], however there have been no methods developed to extract information about the radiometabolites directly from PET data. This PhD aims to develop a new method for non-invasive radiometabolite analysis to allow for the accurate quantification of PET data directly from the PET image and time activity curves. This

PhD will take advantage of more recently developed technology such as total body PET

and PET-MR to investigate novel techniques. Firstly, I will undertake an thorough assessment and comparison of different input function derivation methods and models in place using existing [18F]SynVesT-1 (see Chapter 7.1.1) data for the brain. I will carry out gold-standard analysis as well as undertaking methods to produce image-derived whole blood curves.

I will then compare the kinetic modelling outcomes from these different input function deriving methodologies and subsequently compare these to using whole blood curves only to assess the bias in the metabolite correction. This comparison will be carried out for a range of methods and will enable me to understand current methods and their pitfalls. Following aim 1, I will explore the potential for total body PET to provide the radiometabolite correction needed to produce an accurate input function.

Gathering information from the total body PET scans will potentially allow for relationships between organs and metabolites to be established. The ideal outcome of this aim would be to understand information that total-body PET provides which can prevent the need for arterial blood sampling during PET studies. Following the investigation revolving around PET only data, I shall be investigating MR techniques with the aim of providing either direct or indirect information about the quantity of radiometabolites circulating the body.

MR may also allow for the specific radiometabolites produced post injection to be identified using spectroscopy. This investigation could provide parameters of interest which allow for the radiometabolites to be established directly from a PET-MR scan. Using all the information gathered from the previous aims on current input function derivation methods, total body PET relations and potential MRI methods investigated to develop a model which can derive a free radiometabolite corrected input function directly from an image.

Whether that image will be required to be PET only or PET-MRI will depend on the success on prior aims. This method will then need to validated and shall be tested on another tracer which has a different radiometabolite profile - [18F ]LW223.