by Keith Loria

[This report originally ran in the June 2008 edition of DOTmed Business News]

Did you know that fluorodioxyglucose (FDG) could be called the molecule of the century - both this one and the last?At least it is to anyone who has anything to do with nuclear medicine, or anyone who is suffering from an oncological,
cardiological or neurological disease.

FDG is by far the leading radiotracer (also known as radiopharmaceuticals, biomarkers, and probes), used in PETimaging or PET scans (PET stands for position emission tomography). Because FDG is glucose based, it images the metabolic activity of cells. One reason it is so effective in revealing malignancies is that cancer cells are more metabolically active than normal, adjacent cells, so the tumor shows up as a hot spot. FDG is also useful in evaluating various neurological disorders (such as Parkinson's and Alzheimer's) and cardiac disorders, among others.

"FDG concentrations correlate very well with key biochemical processes," explained Dr. Henry Wagner, Jr., a recognized authority on nuclear medicine and molecular imaging. "What an FDG-PET scan reveals can then be linked to surgical
decision making. What's more, FGD is easy to synthesize, and it has a two-and-a-half hour half-life, which means you can distribute it from one location throughout an entire city."

Wagner explains that because PET scans examine the biology of cells at the molecular level, the presence of cancer and other diseases can be discovered before any symptoms appear, or before any anatomical changes are visible.

PET/CT imaging combines the biological functioning of the patient (the PET part) with a CT image of the body's structural detail. PET/CT technology improves the diagnostic accuracy and treatment management of patients by providing surgeons, radiation oncologists and other physicians with precise anatomical landmarks associated with a disease.

Robert Ranieri, Vice President of Sales at Biodex Medical Systems, Inc., Shirley, NY- a company with a division that makes equipment to store, transport and administer radiopharmaceuticals - noted that "an FDG-PET image can also detect subtle metabolic changes to determine if a disease is active or dormant. It can be used to determine if a tumor is benign or malignant and may be used to stage certain types of cancer."

A PET scan can do more than image the final destination of a tracer. During the scan - which can last a half hour or more - radioactive signals from the tracer can be continuously tracked, revealing its concentration and movement through the body. The data can be used to reconstruct three-dimensional images showing where the compound goes in the body/brain, and how long it stays there (up to the effective useful half-life of the tracer.)

Comparably, SPECT (single-photon emission computed tomography) imaging acquires information on the concentration of radionuclides introduced to the patient's body, providing information which is typically presented as cross-sectional lices through the patient, which can be freely reformatted or manipulated to produce 3D images, just as with PET scans, a SPECT scan is often used to analyze blood flow to any given organ to help determine how well it is functioning, and for a variety of cardiac diseases.

Although SPECT and PET scans are mostly used today to image tumors and the heart, there are more and more studies and scans being done on the brain, as of late.

"The big two right now are oncology and cardiology, which are both being well accepted,"Wagner says. "The brain is the next big one that will gain support, and that's not too far in the future."

By improving diagnosis, PET scans aid physicians in selecting better courses of treatment, as well as assessing whether treatment is effective or should be changed. Recent published clinical trials have shown that in a wide array of cancers, the use of PET has caused the treatment to be changed for 15% to 50% of patients, depending on the specific clinical question. In addition, PET and PET/CT provide both the patient and their physician with a degree of certainty that is often unavailable through other imaging methods.

Since a radiotracer can go just about anywhere inside the human body, the possibilities of what can be imaged is endless, as the biology and chemistry are almost limitless. The body runs on molecules, so in theory, there are an unlimited number of tracers that can be developed. "But you have to develop the chemical synthesis, you have to pick the right ones, you have to get the financial support to develop it, you have to get the approval," as Dr.Wagner notes.

"We expect that PET will open new doors in understanding the pathologies and progression of various neurological disorders like Alzheimer's, Parkinson's, epilepsy, depression and schizophrenia," says Bernd J. Pichler, head of the Laboratory for Preclinical Imaging and Imaging Technology in the Department of Radiology at the University of Tuebingen in Germany, in an e-mail.

Why aren't more radiotracers coming onto the market?

"One big limiting factor right now is regulation by the FDA," Dr. Wagner says. "The problem is that their mindset is so linked to therapeutic drugs, that they cannot simplify things enough to make them appropriate for non-toxic drugs that are administered once to acquire information."

Another big factor is, "the pharmaceutical industry is interested in blockbuster drugs, not diagnostic tracers, they don't put the importance of radiopharmaceuticals where they should be," Dr. Wagner asserts. For example, if you introduce a diagnostic PET tracer, it costs $500,000 just to do the toxicity testing, even though you're giving 1/100th or 1/500th of the toxic dose.

"The core problem is it costs tens of millions to get one of these new PET agents approved for clinical use," Wagner notes, "and there's nowhere the profit in radiotracers that there is in, say, a cholesterol-reducing drug. Big Pharma is interested in billion dollar drugs, so they don't put the money into diagnostic radiotracers. It really needs to be done by small companies."

Unless something changes with Big Pharma, radiotracers are going to need legislative support with the financial funding behind it and heavy promotion by the industry before the FDA approves it.

It is somewhat ironic, as Dr.Wagner noted, that Big Pharma is using PET studies in development of new blockbuster drugs. By turning the drug into a radiotracer, PET scans let researchers see which formulations are absorbed the best and work the best.

The DRA-effect

In predicting what will happen next in the area of nuclear medicine, Alexander J. (Sandy) McEwan, President of the SNM, observed, "the DRA, which clearly has impacted all modes of imaging, is significantly affecting the way in which new technology is going to be introduced. For example, FDG-PET scanning at the moment is broadly accepted, but CMS [Medicare/Medicaid] is currently re-evaluating the next generation of tests."

The current probes look at glucose metabolism, but the plan is to develop probes to examine other parameters of disease activity-such as proliferation, hypoxia, and receptor status. "Over the course of the next few years you will see clinical trials started that will look at what we think is the next generation of probes," McEwan observed, "and then hopefully over the next 5-10 years you'll see those new probes introduced."

The challenge, as McEwan put it, is to find a way for the healthcare community, industry, academia, and the clinical community to work together to get CMS to look favorably on those probes, so they actually get put into use.

Growth in the industry

One of the biggest things to happen in the field of molecular imaging in the past few years is the acquisition of CTI Molecular Imaging by Siemens in 2005.

"When we acquired CTI molecular imaging we spent $1 billion for it," says Markus Lusser, Vice President of Sales & Marketing for the Siemens Medical Solutions Nuclear Medicine Group. "We expanded our product portfolio not only in the traditional equipment side, but we invested into biomarker research. We aggressively invested into preclinical imaging as well as the largest distribution network for biomarkers, a clear sign of our commitment in the molecular imaging arena and especially biomarker development. There are early signs that in the future there will be many biomarkers for certain indications
and clinical questions not only in the diagnostic field but also in the therapeutic field."

A year earlier, GE purchased Amersham, a London-based radiopharmaceutical R&D company that was combined with GE Medical Systems to create a new division called GE Healthcare Technologies.

That acquisition "accelerated the development of molecular imaging and personalized medicine where it will be possible to predict and treat disease with therapies tailored to the individual," Jeffrey Immelt, GE's chairman and CEO, said in a release at the time of the purchase.

Siemens currently has more than 45 radiopharmaceutical distribution centers across the country and are able to ship to roughly 99% of all hospitals in the U.S.

"We are one of the only companies with nationwide distribution of [PET] radiopharmaceuticals and this brings us extremely close to the customer and shows Siemens' commitment to the business because we currently offer clinical imaging equipment, research equipment, biomarkers and even a nationwide distribution network," says Lusser.

Tara Schumacher, a spokesperson for Cardinal Health - which is a global manufacturer and distributor of medical and surgical supplies and technologies - says Cardinal is the leading distributor of PET and SPECT radiopharmaceuticals
for nuclear medicine in the U.S., with over 150 radiopharmacies located across the country.

Dr. Wagner feels the benefits of nuclear medicine are so important that, "the major message I would give is that every hospital above a really small size, those with 100 beds or more, should have a radiopharmacy and the ability to make these tracers locally." Wagner added, however, "the time frame for this happening is going to be long, in the range of 20-30 years; everything to do with radiopharmaceuticals takes longer than you think."

The cost for these small, local radiopharmacies could be as low as $250,000 in upfront money for the equipment. Then you would need to pay for individual tracers and hire staff who are well versed in nuclear medicine.

Today PET is predominantly utilized as a diagnostic tool with one biomarker - FDG - but in the future, because the ability to create a variety of biomarkers for very specific indications of specific diseases exists, the potential is limitless.