Evaluation of the impact of low activity imaging in [11C]-(+)-PHNO and [11C]UCB-J PET-MR scans.

Abstract

Introduction: Positron Emission Tomography (PET) imaging is a close ally of Precision Medicine, and it has been proven to be indispensable in the field of Psychiatry. This imaging modality may also present an important role in understanding Neurodevelopmental disorders and their link to Psychiatric conditions, with new highly selective binders being used currently in research. PET imaging requires the administration of radiopharmaceuticals, where the radioisotope is in incorporated into a highly selective binder. Dosimetry and injected activity optimisation play a crucial role in the field of PET imaging as they allow to determine the radiation dose absorbed by target and non-target tissues, and determine the lowest amount required to deliver images with diagnostic quality and obtain reliable quantitative data, without overexposing patients. The aim of this research is to investigate the feasibility of reducing the injected activity of the [¹¹C]-(+)-PHNO and [¹¹C]UCB-J radiopharmaceuticals, for patients with neurodevelopmental disorders who undergo brain imaging in the PET-Magnetic Resonance (MR) scanner, without compromising quantitative accuracy of outcome measures.

Results: No statistically significant differences were found when comparing the 1/2 to 1/6 datasets with the full injected activity [¹¹C]-(+)-PHNO dataset. Furthermore, the findings obtained from investigating the impact of low injected activity administrations of [¹¹C]UCB-J revealed that it is possible to reduce the administered activity by 1/2, when the clinical outcome measure under evaluation is the binding potential relative to non-displaceable volume (BP_ND). When the outcome measure under investigation is the standard uptake volume ratio (SUV_R), it is possible to decrease the injected activity to 1/3, for [¹¹C]UCB-J.

Conclusions: The simulation and analysis methodologies deployed in this project are suitable for investigating scans with low injected activity for tracers with cortical and striatal uptake, when the outcome measure assessed is the BP_ND or the SUV_R. Whilst the data suggests that imaging with low injected activity is achievable, the efficacy of the investigation is highly dependent on the algorithm used to reconstruct the images, the outcome measure and the radiopharmaceutical used to acquire the PET-MR scans. For the [¹¹C]UCB-J radiopharmaceutical, it is possible to decrease the injectable activity to 1/3 of the original administration without compromising the SUV_R.