Current Research

Drs. Jeanne Link and Kenneth Krohn are experts in radiochemistry, PET imaging and data analysis and bring decades of experience in advising scientists on how using PET tracers can expand their research. They have a track record of major research support for incorporating PET imaging and provide support for integrating imaging into the research of other investigators. Current research at OHSU utilizes radiochemistry in order to drive discoveries in oncology, neurology, pharmacology, cardiology, regenerative medicine, circadian rhythms, metabolism, infectious disease and more.

Our imaging agents involve labeling small amounts (ng-µgs) of material for which we know the precise amount of radioactivity per amount of mass. Images from the PET scanner report radioactivity/voxel in the image so that the result is a quantitative measure in molar units of the concentration of tracer in a given tissue for selected time intervals. This leads to measures such as receptor density or metabolic rates in pmol/L or flow as mL/sec/cm3 of tissue. This capability is very sensitive, specific and unique among the total body imaging tools.

The short lifetime of many of our imaging agents adds the potential to do repeat studies in a single imaging session. For example, we can measure myocardial perfusion before and after exercise, metabolism before and after a drug orpre-synaptic and post-synaptic function of the sympathetic nervous system. Many of these experiments use 11C-labeled radiopharmaceuticals (T1/2 = 20 min) so most of the injected radioactivity is gone within an hour.

Current areas of research

Response to cancer therapy - OHSU collaborators include Drs. Arthur Hung, Christie Binder, and Jeffrey Stevens

PET imaging commonly uses 18F labeled glucose, FDG, a measure of energy utilization and a measure of response to cancer therapy. However, many factors influence energy utilization. An 18F labeled nucleoside, one of the building blocks for DNA, is a more specific measure of tumor growth inhibition after successful therapy. This project will use [18F]-fluorothymidine, FLT, to measure how well sarcoma responds to therapy.

Imaging vascular receptor - OHSU collaborators include Drs. Nabil Alkayed and Sanjiv Kaul

This work entails imaging studies of mechanisms G-protein coupled receptors in the complex molecular signals that regulate local tissue function and response to disease. The focus is on two closely related metabolites of arachidonic acid, a 20-carbon fatty acid with four internal cis-double bonds. OHSU investigators have identified an orphan receptor that is a ligand for two endogenous eicosanoids, one that stimulates increased intracellular calcium in vascular smooth muscle cells and one that inhibits the action. These are basic studies of cardiovascular physiology in disease.

Imaging and assessing inflammation - OHSU and VA Hospital collaborators include Drs. Milky Kohno, Rebecca Spain, William Hoffman, Aaron Janowsky, Jacob Raber, and Lisa Coussens

Inflammation is a biological reaction to tissue damage. In the case of wound healing, it is a highly beneficial process. In other settings where the inflammatory process goes unchecked, it can be highly destructive. This process can be imaged using a 11C labeled drug, PBR28, that binds to a small translocator protein that has high levels as a result of drug addiction [studies by Kohno, Janowsky, Hoffman) or multiple sclerosis (R Spain) or neurodegenerative diseases such as Alzheimers (J Raber). Other projects will image the biology of macrophages and why they sometimes act to cure cancer and sometimes exacerbate it in mechanisms that can be inhibited by antibodies (L Coussens).

Imaging chronic hypoxia and response to therapy - OHSU collaborators include Drs. Jonathan Lindner and Ramon Barrajas

Oxygen is a critical nutrient for cellular energy metabolism and the absence of an adequate oxygen supply has many detrimental consequences. Some of these include ischemic effects, reduced delivery of oxygen, in muscle or brain (stroke). In tumors that outgrow their oxygen supply, genomic changes occur that help the tumor cells survive, proliferate and metastasize, which will be studied through imaging hypoxia in brain tumors. Additional studies are being done to image hypoxia in skeletal muscle. In both studies the PET imaging agent is 18F labeled fluoromisonidazole, a small molecule that is retained in an inverse correlation with oxygen levels in tissues.

Opportunities

Postdoctoral, student and other research positions and training opportunities are available within the Center for Radiochemistry Research. Please contact Hope Phillips at phillhop@ohsu.edu to inquire about current opportunities.