Research Projects

Project summary The neuroinflammation leads to the activation of the microglia, reactive astrocytes, as well as alteration of the blood-brain barrier, which represents the resident immune cell response to the injury in the CNS. The role of neuroinflammation in various diseases has shifted the management of treatment towards it. The paradigm has shifted towards targeted treatment, towards neuroinflammation, and strategies designed for quantifying the area of neuroinflammation using positron emission tomography (PET) and magnetic resonance (MR) imaging to assess treatment response. Our lab is actively working on exploring the role of neuroinflammation in detecting neurodisorders. COX-1 and COX-2 convert the arachidonic acid to prostaglandin H2 (PGH2). PGH2 may play different roles depending on the physiological location. It converts to thromboxane A2 (TXA2)on the platelet surface, whereas it converts to prostaglandin I2 (PGI2). Platelet major contains COX-1, whereas vascular endothelium contains primarily COX-2. There are several reports that insist on the localization of COX-1 in microglia and COX-2 in neurons. Therefore, the quest for new tracers for imaging neuroinflammation is still on. Several radiotracers targeting COX-1 (like 11C-ketoprofen, 11C-PS13) and COX-2 (11C-PS1) have been developed to image neuroinflammation. One of the major limitations with new tracers is that they are not available for imaging in developing countries including India, or these are very expensive to afford in clinical setup in our country. Therefore, we need to develop our own radiotracer, which is produced locally and is economical to produce at the site. The main aim of the study is to validate a lab-synthesised radiotracer [11C]methacetin for neuroinflammation imaging. We will test the specificity of the [11C]methacetin for COX-1 and COX-2 targets in mouse models. We have started neuroinflammation imaging (TSPO PET) using [11C]PBR28 in humans as a part of the project and evaluating its efficacy in amyotrophic lateral sclerosis (ALS) and movement disorders patients (including PD, MSA, PSP). We have an in-house cyclotron, radiochemistry, quality control lab, cell culture lab, small animal (PET-MR) imaging facility, along with a clinical (PET-MR) system for human scanning. We have all the resources to translate our preclinical research into humans using a scientific bench-to-bedside approach. To the best of our knowledge, no other institute has tested a similar radiopharmaceutical in India. Hypothesis of the project: COX-1 and COX-2 are considered biomarkers for neuroinflammation and catalyse the rate-limiting step in the production of the proinflammatory mediators. Therefore, radiolabeled molecules targeting COX-1 or COX-2 can be a biomarker for the early and accurate detection and characterisation of neuroinflammation in the brain. We will explore the potential of [11C]methacetin for targeting COX-1 and 2 targets and compare it with TSPO targeting radiopharmaceuticals like [11C]PBR28. The methodology will involve PET-MR imaging of the mouse model with standard and novel (developed at our lab) radiopharmaceuticals to diagnose neuroinflammation in mice. The project focused on developing an indigenous non-invasive technique to diagnose a disorder at the initial stage by imaging the neuroinflammation.