RESEARCH PROJECTS

Established in 2018, our independent radiochemistry lab has strived to improve the understanding of neurological disease and disorders through PET radioligand discovery and improved production methods. We have a variety of ongoing projects along the translational spectrum.

FABP3 TARGETED RADIOLIGANDS

Fatty acid binding protein 3 transports polyunsaturated fatty acids within the brain and is also a putative α-synuclein chaperone protein. We are interested in FABP3 as a target due to human and animal data showing co-expression with α-synuclein aggregates. These aggregates for Lewy bodies which are pathological hallmarks of Parkinson's disease or Dementia with Lewy Bodies (DLB). Genetic knock-out and pharmacological blockade of FABP3 has been shown to ameliorate motor and cognitive deficits in Lewy body animal models. This project involves library synthesis, radiolabeling, in vitro and in vivo evaluation. By developing an effective FABP3 radioligand, we hope to elucidate the role of FABP3 in neurodegenerative diseases in living brains.

General Radiotracer development scheme

CARBON-11 RADIOCHEMISTRY

The ubiquitous presence of carbon in small molecule exogenous compounds makes it attractive for isotopic labeling. Carbon-11 radiochemistry, despite its relatively short half-life, offers numerous opportunities for tagging molecules with a positron emitter. Nucleophilic [11C]methylations with [11C]CH3I or [11C]CH3OTf have long been used to generate some of the most prominent radiotracers.  To expand this field, we seek to build upon a strong foundation of [11C]CO2 radiochemistry and advance mild reduction chemistries. These will permit robust amide reductions to access heteroatom-alkyl chains longer than methyl and for direct methylation of amines through fixation-reduction mechanisms. Moreover, we are seeking to improve the production and expand the reaction scope of underutilized synthons (CH3NO2, CH2O, CHF3, or CF2O).

Lawson's FXc

IMPROVED ACCESS TO NEUROIMAGING

High infrastructure costs limits PET to large population areas; thus, patients not located near major research centres may have trouble accessing these tests or cannot readily be recruited into large research studies (i.e. ADNI). This excludes an important cohort from these seminal studies and creates health care disparity. We are investigating barriers to accessing PET technology by rural residents of Canada. To truly evaluate, a direct comparison is needed between SPECT alternatives to gold standard PET probes is needed, however, the former do not exist. Some promising examples were recently reported but have yet to be replicated. Our short-term contribution to this area is to replicate these studies and further evaluate candidate SPECT radiotracers in animal models. Long term, SPECT alternatives for as many protein targets as possible will be generated to minimize barriers to accessing nuclear molecular neuroimaging.

SPECT alternatives to PET AD probes

AUTOMATION AND RADIOPHARMACUETICAL TRANSLATION

As part of an interdisciplinary team of molecular imaging scientists and clinicians, we are often tasked with translating radiopharmaceuticals from other sites. Either for preclinical or clinical applications, these new-to-us radiopharmaceuticals require optimization for our equipment and site set up. To meet the ever growing library (and regulatory) demands, we are constantly exploring was to improve radiolabeling efficacy and robustness. To date, these efforts have focused upon very short half-life products such as O-15 water and N-13 ammonia. We have built an automated purification system and adapted commercial quality testing equipment to streamline production processes and make them more reliable. Readily available microprocessing boards, such as Arduino and Raspberry Pi, and on-site 3D printing makes for practical, low-cost, and near limitless laboratory optimization.

NH3_Sketch3.png
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FUNDING

  • Lawson Health Research Institute Internal Research Fund

  • Saint Joseph's Health Care London Foundation; Fiona Monckton Fund

  • Canadian Institute for Health Research

  • New Frontier in Research Fund - Exploration

  • BrainsCAN (Canada First Research Excellence Fund)

  • Canadian Foundation for Innovation

  • Schulich School of Medicine and Dentistry, Western University Collaborative Research Grant

  • Academic Medical Organizations of Southern Ontario

  • Joint Programme - Neurodegenerative Disease Research