Across the Bench with Amanda Freise

This is an Across the Bench piece! Check out Amanda's interview of Laura here!

 

In the Wu Lab (part of the Crump Institute for Molecular Imaging at UCLA), researchers are working to find new ways to diagnose immune diseases by studying the way that disease develops in healthy tissues. The goal is to find painless, non-invasive ways to identify diseased cells in patients. I sat down with Amanda Freise, a graduate student researcher in the Wu Lab, to understand just how that works.

 

 

The Wu Lab uses molecular imaging in order to study diseased tissues. Traditionally, scientists would use imaging techniques such as X-rays, CT scans, or ultrasounds to take pictures of physical structures in the body. But, in order to see and measure ongoing biochemical processes, molecular imaging must be used.

 

"Molecular imaging is not just looking at anatomy; it's about looking at biological markers or processes," says Freise, whose research focuses on a particular type of molecular imaging called PET scanning. "We look at the molecular characteristics of cells."

 

How do you take a molecular image? First, you have to choose a tracer - that is, a molecule that will seek out and identify the cells you want to take a picture of. There are several ways to do this. You could try using a molecule that the target cells like to metabolize. Cancer cells, for instance, love to metabolize glucose. That means that glucose, when injected into the body, will show up more often near the cancer cells than any other cell.
A patient's brain (with a tumor) after being injected with radioactively tagged glucose molecules. While the glucose spreads throughout the brain, it concentrates near the tumor.


One potential issue with glucose is that it's not just metabolized by cancer cells, so it also gets used by other cells, albeit to a lesser extent. When you then try to take a picture, you'll get a lot of background noise from the glucose that's not being used up by the cancer cells themselves.

 

Image credit: Anna Tanczos. Wellcome Images. Antibodies bind to proteins on the surface of a cell.

Image credit: Anna Tanczos. Wellcome Images. Antibodies bind to proteins on the surface of a cell.

 

The Anna Wu Lab at UCLA is trying a different approach to molecular imaging. They use special types of proteins called antibodies. Antibodies are specialized proteins that seek out and neutralize foreign molecules in the body in order to fight disease. A healthy adult has millions of these antibodies in their bodies. The advantage of using antibodies instead of glucose is that a particular antibody will only bind to one other specific protein, which cuts down on the problem of background noise in the image.

 

Freise and her colleagues need to make sure that the antibodies will bind to the proteins they actually want to find. To figure out the exact DNA code for the antibodies they want to use, they have to create and test different antibodies by cutting and pasting DNA with enzymes until they have engineered the perfect antibody for the job at hand. They then insert the DNA blueprint into cells in a petri dish, and wait for the cells to do what cells do: make proteins. Effectively, they design blueprints for the perfect antibody, then use cells (which, in turn, use those blueprints) to clone the antibodies and create a sample they can use.

 

Once they have a sample of antibodies, they then tag the antibodies with radioactive atoms. This is what makes it possible to actually take a picture of the antibodies once they are in the body. These radioactive isotopes give off positrons as they decay. Positrons are like electrons, but with positive charge instead of negative charge. When a positron collides with an electron, they annihilate each other, releasing energy in the form of photons. Taking a picture of these photons is called Positron Emission Tomography, or PET.

 

The problem with antibodies is that, even though they do only bind to one protein, they have other functions besides just binding to things. That means that, on their way to the target cells, they will also float around in other parts of the body, creating the same background noise problem that existed for the glucose tracer. In addition, researchers want to cut down on the length of time that these radioactive tags are floating around in the body while scientists wait for the background noise to die down.

 

What the Wu Lab specializes in is breaking apart the antibodies into fragments, and only using the part of the antibody responsible for the binding process in molecular imaging. That means that the antibody won't float around the body aimlessly for any length of time, and will instead go straight to the target cells.

 

What's really incredible about this project is that all parts of the project are done in-house at UCLA. The Crump Institute is a multidisciplinary group of several individual labs, all working on a piece of the puzzle of molecular imaging. There's one lab that makes the machines used in other labs (such as the PET scanners themselves). Another lab focuses on producing the radioactive isotope tags for the antibodies.

 

"It's really amazing to be able to image a process, or image a single molecule of interest, because the body is so complex", says Freise.

- Laura Haney (@LauraVican)

Signal to Noise co-founder and COO

PhD Candidate, Physics and Astronomy