The North American nuclear medicine/radiopharmaceuticals market was worth almost $2 billion in 2015 and is expected to reach about $3 billion by 2020, according to a market report from Reportlinker. The aging population, growing prevalence of cancer, interest in hybrid imaging, the rise in public awareness, abundance of radiopharmaceuticals and technological advancements are contributing to the growth in the market, according to MD Buyline.

FDG is the most widely used radiopharmaceutical on the market, and with more facilities making it the price is decreasing. Big commercial entities are producing it in larger volumes. “Some academic sites are stepping away from that because the commercial entities can make large batches and can distribute it to the hospitals that need it,” says Suzanne Lapi, president of the Society of Nuclear Medicine and Molecular Imaging’s (SNMMI) Radiopharmaceutical Sciences Council.

The three major companies that produce FDG in North America are Cardinal Health, Isotech and Cambridge Isotope Laboratories, according to MD Buyline. PETNET Solutions, a wholly-owned subsidiary of Siemens Medical Solutions USA, is another manufacturer of FDG and it accounts for more than 90 percent of the products it produces. When CMS introduced the Three Scan Rule in the U.S. about three years ago to limit the number of PET scans a patient can have, the demand for FDG fell.

Volumes growing again
“It created a lot of confusion with imagers and I think that’s what drove some of the market retraction back at that time, but I think that confusion has generally been clarified and people understand it now,” says Barry Scott, CEO of PETNET. “Over the last year and a half, we have started to see FDG volumes slowly growing again.” Reimbursements for radiopharmaceuticals have dropped due to bundled payments. They are now being bundled with some SPECT procedures, so the facilities aren’t receiving separate reimbursement for the radiopharmaceuticals anymore.

“Radiopharmaceutical reimbursements are managed under bundling and charge compression [and] that has lowered the payment and made the true cost of the radiopharmaceutical [unclear],” says John Witkowski, president of United Pharmacy Partners. “Some high-cost radioimmunotherapies have seen lesser utilization due to the radiopharmaceutical cost and the lack of adequate reimbursement.”

It’s well known that PET bone scans and other PET exams have experienced reductions in reimbursement. There are several radiopharmaceuticals that now have reimbursement rates that are less than the cost of the radiopharmaceutical. SNMMI is working to change this by providing education and outreach on how these bundled payments may affect procedures and how the reimbursement should actually be carried out. For example, with PET/CT and PET/MR, SNMMI is trying to educate people on what the true costs are.

Keep your eye on these
Gallium-68 compounds, derived from Germanium-68/Gallium-68 generators, for imaging somatostatin receptors have recently become more prominent, says Lapi. This has the potential to label many ligands and would also offer improved PET imaging capabilities for tumors and other diseases in the future.

Choline C-11 holds promise for cardiac and oncologic use, but more specifically prostate cancer. In November 2015, Zevacor Molecular announced FDA approval of ANDA for Choline C-11, making the company the only approved commercial manufacturer of the radiopharmaceutical. Prostate cancer patients typically are diagnosed through a rectal exam or with a blood test called PSA, which evaluates a specific protein that, when elevated, signifies cancer. When the patient receives the initial treatment, his PSA level usually falls to zero.

Many of the patients often experience some sort of biochemical recurrence after the initial treatment and undergo a bone, CT or MR exam so the physician can determine the location of the cancer. If the physician can’t determine the cancer’s location, the patient will be treated with chemotherapy or radiation of the pelvis. However, the patient may still have cancer in a specific part of the body and it will often go from early-stage to stage 3 or 4 before the physician detects it.

Early detection and treatment
“The whole significance of Choline C-11 is that now we have the tool [with which] we can help identify early recurrence,” says Peter Webner, vice president of clinical development at Zevacor Molecular. “The key to long-term survival is early detection and treatment and, if at all possible, targeted treatment.”

The major challenge with Choline C-11 is that it has a 20-minute half-life, meaning Zevacor has to quickly get it to its customers so they can use it within an hour and a half time frame. Because of that, it has very limited distribution, but Webner believes it’s worth it because it’s a very sensitive product that will help the patients get treated sooner.

Prostate-specific membrane antigen (PSMA) is the ultimate goal for prostate cancer imaging. Webner believes there will be radiopharmaceuticals in the future that will be able to directly localize PSMA, which will help reduce false positives and increase specificity. However, that may not be for several years, so all physicians have for now is Choline C-11. “Every urology group I have spoken with in the past few years said it’s an unmet need for them,” says Webner. “They realize it has its limitations and it’s not a perfect product, but right now there is nothing else for them to use.”

Prevent cardiac death
Iodine-123-MIBG is a newer SPECT radiopharmaceutical that is showing promise in risk stratifying patients with heart failure. Dr. Garima Sharma, a nuclear cardiologist at Johns Hopkins, has firsthand experience with its benefits. “Risk stratifying patients in a better manner can [help us] give patients better medication or a defibrillator and follow them closely to prevent cardiac death,” she says.

Many medical centers in the Midwest have conducted studies using Iodine-123-MIBG. They are trying to determine if they can reduce the need for implantable cardioverter defibrillators (ICDs) in heart failure patients by predicting if they have high sympathetic activity in their heart. (See “Defibrillators: technological advancements are fueling this market segment” at dotmed.com/news/30446.)

A new PET enzyme for radiation therapy planning is currently in the works, but it may take a few years for it to come to market. The reasons it’s taking so long are the lack of reimbursement for PET/CT in radiation therapy, and because PET and CT are performed in different parts of the hospital. However, the demand for those procedures is so high that the reimbursement rate will improve in the years to come, says Jamie Dildy, clinical analyst at MD Buyline.

New 70 MeV cyclotron in town
In September 2015, Zevacor installed the only commercial 70 MeV cyclotron dedicated to medical use in the U.S. The company’s goal is to stabilize the domestic supply of medical isotopes including Strontium-82 for use in the diagnosis of cardiovascular disease. “It’s an interesting space for us because there are all of these population dynamics that we see now as people get older, heavier and tend to get heart disease,” says Webner.

“The biggest challenge for cardiac PET, when you look at the Rubidium generator platform in general, is that there are raw material supply constraints.” Bracco Diagnostics, which generates Rubidium- 82 using Strontium-82, has a shortage of Strontium-82 because the company has consumed all of it. Zevacor is planning on producing an abundant supply of it to support Bracco along with other generator manufacturers when they come online, as well as the U.S. Department of Energy.

The Cyclone 70P was developed by Ion Beam Application and is a high-power proton cyclotron with variable proton acceleration in the energy range of 30 to 70 MeV. The facility that houses the cyclotron is in Noblesville, Indiana, and includes a production center, research and development space, and offices for the staff.

Radiotherapeutics
“I think it’s really exciting because now [the industry has] been talking about theranostics,” says SNMMI’s Lapi. “We can actually start to see this come forward, where we’ve got these compounds that target and report on the expression of a certain receptor that’s in cancer, and then compounds that can target for targeted therapy.”

Following up on this is the use of Lutetium- 177, which is a radiotherapeutic that can be a substitute label to the same Gallium-68 ligand. It creates a therapeutic dose for the tumor and may improve patient outcomes. “Theranostics, using radiopharmaceuticals that allow diagnostic imaging and the same for therapeutics, should provide a variety of radionuclide candidates to the market space,” says United Pharmacy Partners’ Witkowski.

Selling technology
Cancer drugs usually work by immunology, but radiotherapeutics have a much different approach. These drugs produce radiation sources close to the cells and work effectively for certain diseases including non-Hodgkin's lymphoma and blood-borne diseases.

The market is splintered because the commercial base isn’t big enough any longer for the larger companies to make useful investments, says Marvin Burns, president of Bio-Tech Systems, a market research company for the health care industry. At first, the major companies were involved because the drugs were expensive to produce, but they are now selling their products to small specialty pharmacies. “It’s really expanding now as smaller specialty companies are able to get into the field,” says Burns. “Big companies are selling technology to small companies that are [better] positioned to sell the products, and since you don’t need giant biotech [companies] to sell radiotherapeutics.”

Bayer’s Xofigo was introduced about three years ago to treat bone metastases. The radiotherapeutic is injected in the patient’s bone and produces intense energy that kills cancer cells and limits damage to nearby healthy cells. The average price of a yearly supply of Xofigo is about $60,000 per patient. The average price of a year’s supply of conventional cancer drugs is estimated to exceed $100,000, according to the Mayo Clinic.

“[Xofigo] can be viewed as an expensive drug, but it is in the same magnitude compared to some of the novel [chemotherapy drugs],” says Paul-Emmanuel Goethals, co-founder of MEDraysintell, a market research company for radiation health care. Radiotherapeutics made up about 10 percent of the total nuclear medicine market in 2015, and it was largely driven by the success of Xofigo. Goethals expects that radiotherapeutics will represent about 50 percent of the nuclear medicine market by 2030.