John Eisenbrey, PhD, Associate Professor of Radiology and Researcher at the Cancer Center at Thomas Jefferson University talks about Microbubbles.
Interview conducted by Ivanhoe Broadcast News in May 2018.
How did you get the idea for this, how did the idea occur to you? Because they’ve been using this for just sort of a diagnostic method.
Dr. Eisenbrey: Right. Groups have shown in preclinical models only at this point that this popping of bubbles makes tumor blood supplies more sensitive to radiation. And we use these a lot clinically for research and off label as well looking at different liver lesions. And what we saw was that these patients, incidentally we ended up doing a patient or two that were treated with radioembolization and what we were able to show is that the bubbles still actually profused in to those tumors after treatment and we can detect them and we can pop them. The idea essentially came about that we could potentially use this to improve how well liver cancer is responding to radiotherapy in patients.
And what is inside the microbubble?
Dr. Eisenbrey: Inside the microbubble is a high molecular (weight) gas and it’s stabilized by some type of outer fat generally or lipid. And that essentially allows the small gas microbubbles to circulate throughout the blood supply for upwards of five minutes or so before breaking down.
Because you are already using this diagnostically you didn’t have to think of some new gas to put in there right?
Dr. Eisenbrey: Right. So we spent about two years showing that this was effective for treating liver cancer in some of our preclinical models. But what’s nice about using a drug that’s already approved for other applications is it allowed us to navigate the FDA process relatively quickly. We were able to get kind of to this point where we’re now in the first of human’s trial and hopefully showing therapeutic benefit pretty quickly.
Walk us through how it goes in with the saline injection and how they travel to the site to work with the beads.
Dr. Eisenbrey: Sure. We put a small catheter in the patient’s arm in the vein. We mix up these micro-bubbles with about fifty milliliters of saline and we just infuse this over a ten minute period. The bubbles infuse in to the vein and they go into the vascular system and they actually circulate everywhere in the body. What the ultrasound does is that we can focus our ultrasound beam only on the liver tumor. While the bubbles are circulating everywhere in the body we can use the ultrasound and focus that just on the tumor itself and pop the bubbles only within the tumor or that surrounding area.
Is the ultrasound doing anything other than that? Is it delivering the radiation against the tumor at the same time?
Dr. Eisenbrey: There’s been a little bit of work showing that there is some minor therapeutic benefits of this level of ultrasound in tumors. But for this particular study we’re only using the ultrasound to pop those bubbles within the tumor. And the hope is that popping mechanism actually makes the blood vessels more sensitive to the radiation that our colleagues in interventional radiology are placing within the tumor.
So right now you’re not using those simultaneously, the radioactive beads and the bubbles?
Dr. Eisenbrey: The radioactivity is actually placed within the tumor by our colleagues in interventional radiology roughly two hours prior to our first bubble study. And what essentially happens is our interventional radiology colleagues put these glass beads inside the tumor with a catheter. And that glass bead, they’re called radiospheres or TheraSpheres that provides a sustained release of radiation within the tumor. There’s actually active radioactivity within the tumor itself for ten days following that placement of those beads.
So it’s still working?
Dr. Eisenbrey: It’s still working.
The gift that keeps on giving.
Dr. Eisenbrey: Hopefully, hopefully. And it’s localized. By getting access just to the tumor blood supply with the catheter and depositing the beads only within the tumor the hope is we’re cooking those tumors but not the surrounding liver. Not the healthy tissue.
A couple of things here, It’s a much more direct delivery method to keep it isolated to where the tumor is.
Dr. Eisenbrey: Absolutely.
And they’re acting as helper bees together these two, the radioactive beads and the bubbles?
Dr. Eisenbrey: That’s correct, yes.
So how are the glass beads delivering that radiation to the tumor?
Dr. Eisenbrey: The beads themselves are a therapeutic product that’s now available and they have Y90 radiation embedded within the glass beads. And our interventional radiology colleagues will essentially get access by the femoral artery. They’ll take a very small catheter and they’ll go up the femoral artery, they’ll work their way through the body until they get access to the feeding blood supply of the tumor. And once they confirm that they’re in that location they can deposit those beads just inside the tumor sparing the rest of the body of that radiation.
How many times have you done this?
Dr. Eisenbrey: Done this procedure with the microbubbles?
Yeah.
Dr. Eisenbrey: Right now we’ve enrolled ten patients, the goal is to enroll fifty two patients over the next two years or so. And hopefully our results stay as positive as they have been to date.
Talk about the results that you’ve seen to date.
Dr. Eisenbrey: Sure. We’ve enrolled ten patients as I said. The first primary objective was to show that this was a safe technique using bubbles which is what we’ve done. And now we’re looking at how effective it is. And to date it’s early in the study we’re only about ten to fifteen percent of the way through. But we’ve shown that patients who are getting bubbles, their tumors are responding better to the radiation therapy. We see more complete response and the hope is that we get more patients to full liver transplant and ultimately cure their disease.
When you say responding better how do you mean that?
- Eisenbrey: When we talk about early response to the treatment of radioembolization we’re talking about complete reduction of tumor vascularity and then ultimately shrinking of that tumor in terms of volume as well.
Because as we were talking before tumors are hypoxic is the term I guess?
Dr. Eisenbrey: They are, yes.
They’re dense?
Dr. Eisenbrey: They’re dense, they’re hypoxic but they still have active blood supply. The hope with a lot of these therapies is you first destroy that blood supply and that essentially starves the tumor and then it begins to shrink over time.
What did you think to yourself the first time you actually saw it work?
Dr. Eisenbrey: Well the first time we saw it we thought we might have gotten lucky so we continued to enroll patients. But I think the feeling now is that we believe this has a very good chance of actually working and helping patients. And as an engineer and as a researcher it’s nice to be in a clinical environment where you can finally get to see some of this technology and some of this research translate to actual patient benefit.
Because liver cancer as we know is?
Dr. Eisenbrey: Liver cancer is increasingly becoming one of the most leading causes of cancer mortality worldwide. And these rates are increasing particularly within the United States as well and that is mainly attributed to Hepatitis C epidemic. It’s estimated that we now have up to three and a half million Americans living in the United States with Hepatitis C. And most of those patients are more or less asymptomatic and don’t even know that they have the virus. They will live for decades with no knowledge that they are actually carrying this disease.
What about fatty liver and stiff liver and all that?
Dr. Eisenbrey: Sure. So fatty liver is becoming increasingly common because of the epidemic of poor diet. I think Dr. Civan will talk a little bit about that. So we’re starting to see more liver cancer cases coming up as a result of fatty liver. That is definitely on the horizon of something that’s probably going to overtake Hepatitis C as one of the leading causes for liver disease. But at this point we’re primarily still seeing Hepatitis C.
I know you’re just beginning of the trials and everything, but can you see some far reaching other materials that you might put inside those microbubbles?
Dr. Eisenbrey: Sure. We are actively involved in not only using these microbubbles off label that are clinically approved for making our own. And we work with chemists over at Drexel and some of our own engineers here at Jefferson to put different molecules of interest inside the bubbles. We’ve put chemotherapy drugs inside the bubbles, we’ve put oxygen to improve radio sensitivity to tumors. The thought then is that you could inject these bubbles and they would circulate throughout the body like they normally do but not only would we pop the bubbles inside those blood vessels and sensitize those vessels but we could also potentially locally release a drug or bioactive molecule of our choice just inside the tumor.
Do you think it’s the popping, is it the shock of that? What is it that’s causing the reaction?
Dr. Eisenbrey: It is. Groups have looked at this and they’ve shown that that popping is actually necessary for sensitizing malignant tissue to radiation. We call that inertial cavitation where the bubble will essentially oscillate so it will expand and contract and then eventually it will pop. And there’s a lot of localized energy in that popping mechanism. And that is the mechanism that sensitizes the tumor to radiation.
Would it be motion or energy?
Dr. Eisenbrey: Energy.
Energy?
Dr. Eisenbrey: Yes. It’s very localized and it’s very short lived but it is a high amount of energy when that bubble actually cavitates with the tumor blood supply.
Groundbreaking isn’t the right word but it has such far reaching parameters in dangerous cancer.
Dr. Eisenbrey: It is yeah. We’re looking at a lot of different cancer applications and ways that we can move this forward. For example, we’re looking now at external beam radiation with breast cancer and maybe some head and neck cancers. And I also have a colleague who is looking at using this phenomenon with chemotherapy to improve treatment of hopefully patients with pancreatic cancer.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Jessica Lopez, Media Relations
215-955-5291
Sign up for a free weekly e-mail on Medical Breakthroughs called
First to Know by clicking here.
