Illustration depicting current PET scanners (left) and total-body PET (TB-PET) scanners (right). [Credit: S.R. Cherry et al., Science Translational Medicine (2017)]

Ten years in the making, researchers have finally received funding to build a prototype of the world’s first total body positron emission tomography (PET) scanner. The development could potentially significantly alter medical imaging and help advance a number of areas of biomedical research, including oncology, drug development and maternal-fetal studies, according to scientists involved in building the device. 

The project is co-led by Simon R. Cherry, Ph.D., professor of biomedical engineering and radiology at the University of California, Davis, and Ramsey Badawi, Ph.D., also a professor of radiology and biomedical engineering and Chief of Nuclear Medicine at UC Davis.

PET scanners already provide a great insight into tissues and organs, so what inspired researchers to undertake the huge project of developing a full body PET scanner?

“[It was] the realization that we are missing so much of the available signal,” Cherry told Bioscience Technology. “And the growing appreciation that many diseases and disorders involve multiple organs and systems in the body.” There also aren’t any current imaging tools that can look at function in the entire body, he added. 

With the new technology it’s possible to see all organs and tissues in the body at once and track what is happening everywhere, Cherry said.

Unlike traditional PET scanners, which provide a narrow view of tissue, the new scanner can produce a broader image, but at a much higher resolution image of the body’s organs. 

“This could allow us to collect images much more rapidly – dramatically reducing blurring caused by motion of the subject during the scan,” Cherry said.

Another added benefit is that much lower doses of radioactive tracers are needed than conventional scanners, opening the door for studies involving sensitive patient populations like pregnant women and children, and safer longer-term scans.

“The reduction on radiation dose will allow us to scan the same subject repeatedly over a long period, so that we can better determine the course, causes and cures of chronic diseases such as arthritis, diabetes and obesity,” Badawi told Bioscience Technology.

Currently, to get a ‘full-body’ scan, researchers must make a composite from serial scans, and also information that comes from measuring temporal changes in radiotracer distribution can only be collected from one part of the body at a time.

“As a result, the full potential of PET as a translational research tool has not yet been realized,” the researchers wrote.

The total body PET scanner would provide a solution, the researchers said, capturing almost all of the emitted photons and providing simultaneous coverage of the entire body, with a greater than 40-fold gain in effective sensitivity and a greater than 6-fold increase in signal-to-noise ratio compared with full-body imaging on conventional PET scanners.

Broad potential applications

The paper, published March 15 in Science Translational Medicine, outlines a variety of potential research and healthcare applications.

Oncology is the first area that the scientists believe this technology could make an impact.

The machine’s increased sensitivity would be able to detect small, low-density tumor deposits known as micrometastases. Currently the standard is that all patients with metastasis risk indicators receive chemotherapy, which can be toxic and expensive, and after which it’s not possible to determine how effective the treatment was, the researchers said.  The total body PET scanner would provide a noninvasive method that could detect these micrometastes, guide clinicians if chemotherapy is appropriate, and be able to assess the therapeutic response.

This work could then extend to investigations into infectious diseases, such as HIV and tuberculosis.

A second application reported in the paper is drug development.  For example, the researchers suggest that high-sensitivity total-body pharmacodynamic investigations could be performed during phase 1 and 2 clinical trials. Pharmacodyamics is the study of how a drug affects an organism.

The ultra-low radiation dose scanning could also support the translation of basic research in maternal-fetal medicine to in-human studies, for example to increase knowledge of fetal distress. It could also advance in vivo brain studies to investigate developmental disorders in children. 

For Cherry, the most exciting applications are the ones that haven’t even been thought of yet.

“I’m sure physicians and researchers will find ways to use this technology we have not even dreamed of, and that will be very exciting,” Cherry said.

Still the area of multisystem disease is an area that piques his interest.

“Based on what we know now, I’m most excited about how we use this technology to study the complex interactions of the brain, gut, microbiome and immune system in a range of neurological and metabolic disorders,” Cherry said. 

Challenges and limitations

While the technology is both promising and exciting, there were challenges in getting to this point and further advances will still be needed before the total body PET scanner can fulfil its potential.

“The scale of the system is enormous by current standards,” Cherry said. The largest technical challenge, he said, was making sure that the vast amounts of data could be collected, moved, stored and processed in a sensible amount of time without any losses.

Interestingly though, in Cherry’s opinion, there was an even larger challenge to overcome.  The biggest challenge was “to convince the biomedical research and clinical community, as well as the funding agencies, that the high initial cost of developing a scanner that covers the entire body is readily justified by the clear opportunities this technology has for contributing important new findings on human health and disease, as well as improvements in patient care,” he said.

The National Institutes of Health awarded $15.5 million to Cherry and Badawi to lead the multi-institutional EXPLORER consortium to build a prototype of the scanner through the NIH Transformative Research Award program.  Cherry anticipates that the first human research subjects will be scanned in mid-to-late 2018. Since clinical use depends on approval from the Food and Drug Administration there is some uncertainty as when the scanner would become available to the public, but Cherry is hopeful that they will be doing clinical scans within three years.

Getting approval is one thing, but making the technology widely available is another. Although the researchers say that the total body PET scanner could have an “immediate impact” by a combination of producing better image quality, and reducing radiation doses and the time it takes to scan, they note that the initial high cost could be prohibitive.  The scanners are projected to cost about five to six times that of conventional scanners. 

Most healthcare centers won’t adopt the technology until either technological advances bring the cost down, or it’s proven that they provide a significant clinical advantage.

An additional initial challenge once the device becomes available is to develop “imaging paradigms that demonstrate its powerful and unique role,” the researchers wrote.  They added that imaging biomarkers will need to be developed so that some of the more advanced applications can be realized.

The massive amounts of data gathered by the scanner will also require analysis methodologies to be developed and refined.

Still, the scientists are hopeful and anticipate, based on earlier evolution of PET technology, a “self-fulfilling process” where research and clinical use will lead to technological advances that lower the cost and propel adoption and use in translational medicine and health care.

Contributing Editor/Science Writer