Image-Guided Chemistry Laboratory (IGCL)

We apply creative chemical strategies and fundamental biophysics principles through in-situ chemistry for local treatment of tumors with minimal or no systemic toxicity. To better understand the effects of such interventions, we use a multidisciplinary approach. We work closely with collaborators in imaging physics and molecular imaging using advanced MR and CT methods to characterize and monitor our interventions. We also employ analytical technologies including mass spectrometry imaging to complement conventional immunohistochemistry and fluorescence microscopy techniques.

The main focus of our lab is liver malignancies, both primary and metastatic. Using common reagents in a thermochemical ablation technique in vivo we have achieved 105°C within seconds. At the same time we have instantly created a local hypertonic environment of 15,000 milliosmolar, yet without adverse systemic effects. In vitro we have readily exceeded 200 °C. The most interesting and clinically significant biology, however, occurs at the margins where temperature and osmotic pressure are less extreme and changes occur more slowly. This is an area we are investigating in great detail as it is where treatment failure and local recurrence happens with conventional ablation methods.

We study combined stress with thermal, osmotic, oxidative and protic (pH) components to identify promising pathways for manipulation and targeting, using imaging to help deconvolute the contributions of each stress. We are also investigating a multiplexed approach using drugs themselves as reagents in exothermic reactions and as imageable theranostic agents. As we improve our knowledge of cytoprotective stress responses, we will be able to manipulate the conditions in the local environment. The insights we gain will help to decrease local recurrence and procedural morbidity while improving outcomes for patients.