When patients come in to Northern California PET Imaging Center in Sacramento,Calif. after receiving troubling cognitive tests, doctors are able to put their worst fears to rest – or help guide them to the right treatment. To date, the facility has performed nearly 30 PET scans using Amyvid, a radiotracer that detects amyloid plaque, which has been identified as an important indicator for predicting Alzheimer’s disease. Amyvid was FDA approved in April 2012.

Still, it’s not yet a perfect science. If the specialist detects plaque, it could be Alzheimer’s or it could be another disease. But if there is no plaque, it’s not Alzheimer’s.

“One of the best indications that the physicians seem to really like is when they’re going down the path thinking it is Alzheimer’s, then we end up with a negative scan, and they can start looking at other causes for the patient’s symptoms that they might be able to help or fix,” says Ruth Tesar, CEO of the imaging center. “They might have depression, anxiety or a different type of dementia.”

Depression, for one, can look similar to Alzheimer’s and dementia in PET scans using the tracer FDG and obviously requires a different course of treatment. While there is no cure for Alzheimer’s, patients whose tests suggest they do have the disease can be prescribed medications that treat systems and slow progress, or make the decision to sign up for experimental treatments.

And more amyloid imaging drugs may be on their way to imaging centers soon: GE’s flutemetamol was accepted for review in January, and Piramal’s florbetaben was accepted in March.

There’s just one problem — while some physicians find Amyvid to be useful in their practices, so far, CMS isn’t convinced. Amyvid has not been approved for reimbursement, with decision makers questioning the scans’ usefulness when little treatment for Alzheimer’s exists. Manufacturers and PET advocates are concerned that CMS’s hesitancy could slow down treatment progress for Alzheimer’s as well as for other tough diseases.

CMS concerns
With the number of people with Alzheimer’s disease expected to triple by 2050, there’s no doubt a wide swath of the aging population would be eager to get a scan when they feel their memory beginning to slip. But should every aging, worried mind go in for amyloid imaging?

That’s one concern that has likely gone into CMS’s decisions so far, Tesar says.

“I think CMS looks at how many people there are worrying about potentially getting Alzheimer’s disease, and it’s probably four to five times the number of patients that actually have it,” says Tesar. “CMS perceives that as very expensive when they are trying to cut costs.”

In January, the Society of Nuclear Medicine and Molecular Imaging (SNMMI) joined with the Alzheimer’s Association to publish appropriate use criteria for amyloid imaging. The groups met with CMS in April to continue making a case for the radioisotopes.

The criteria said it would not be appropriate to scan based solely on family history, for example, but would be appropriate for patients whose clinical tests indicated progressive or persistent cognitive impairment, or whose tests showed the chance of Alzheimer’s but were inconclusive.

“There’s a subsection of the population where this would be useful, and then over time we’ll have to build up evidence on how to really use these tools. Hopefully, we will do that and then have a clear idea of which populations will make the most sense,” says Jonathan Allis, general manager of PET Medical Diagnostics at GE.

PET is a relatively new imaging method, another possible reason CMS has been slow to accept amyloid imaging, and up until now, most PET scans used FDG, which remains the “workhorse” of the industry. When CMS first began reimbursing PET scans around 10 years ago, it explicitly stated non-coverage for future applications of PET. That rule has recently been loosened for new oncology tracers, but not for cardiology and neurology tracers.

“We’re starting with an exclusionary policy, and that makes it an uphill climb,” says Dr. Daniel Skovronsky, CEO of Avid Radiopharmaceuticals and VP of Tailored Therapeutics for Eli Lilly, which manufactures Amyvid.

A new draft decision from CMS is slated to come out in July, followed by a period for public comment.


Beyond the brain
Skovronsky says he’s concerned that a decision not to reimburse Amyvid would discourage innovation in the rest of the radiopharmaceutical industry.

“It takes a long time and a lot of money and perseverance to bring a novel molecular imaging agent to market as we did,” says Skovronsky. “If it’s not covered, I think that could have a very chilling effect on the industry because people will say if even an Alzheimer’s diagnosis is not valued by our society, why should we work on diagnosing any other diseases?”

One of those areas that may be affected is prostate cancer diagnosis and tracking. In March, CMS proposed limiting reimbursement for FDG PET scans for prostate cancer patients. The same decision also limited reimbursement to one scan per patient.

While FDG PET scans have been found to be less useful for the early stages of prostate cancer, they are helpful when evaluating treatment response to metastatic prostate cancer, according to a study published in 2012 in the American Journal of Roentgenology.

“Prostate cancer is heterogeneous, so it’s hard to follow what’s happening with the disease at different times,” says Hossein Jadvar, study author and president of the American College of Nuclear Medicine. “PET imaging can be helpful to stratify patients and do the right thing to the right person at the right time.”

Jadvar and the American College of Nuclear Medicine composed a multiple society letter to CMS encouraging FDG PET reimbursement for prostate cancer.

“We thanked them for reimbursing some, but said that just one scan isn’t enough,” says Jadvar. “And FDG PET does hold value.”

Besides FDG, sodium fluoride has also experienced resurgence as a tracer in bone scanning for metastatic prostate cancer. Such scans can reveal cancers that CT scans miss.

One newly approved imaging agent for prostate cancer treatment is C-11 choline, a tracer developed at the Mayo Clinic that was approved by the FDA in September 2012.

“It’s used for patients who have already been treated for prostate cancer, but tests show that it’s coming back,” says Dr. Timothy DeGrado, president of SNMMI’s Radiopharmaceutical Sciences Council. “A C-11 PET scan has shown to be useful in detecting where that recurrent prostate cancer is.”

In the skin and breast cancer space, Tc 99m (Lymphoseek) recently became the first drug approved for lymph node mapping since 1981. It allows doctors to see if cancer has spread to the lymph nodes and helps them pinpoint and remove the diseased tissue.



Flurpiridaz F 18 is a PET imaging agent being developed by Lantheus that the company says will be used to evaluate cardiac blood flow in patients with known or suspected coronary artery disease. It’s currently in Phase 3 clinical trials.

Another F 18-based isotope, LMI 1195, helps identify candidates for an implantable cardioverter defibrillator to decrease the risk of sudden cardiac death.

"People get them who don't need them, and there are people who need one who don't fit into the categories to get them," says William Dawes, vice president, Manufacturing and Supply Chain of Lantheus Medical Imaging. "There is currently no good test to risk-stratify. LMI 1195 is a novel F 18 small molecule tracer that has the potential to help decrease risk of sudden cardiac death."

If all goes according to plan
Back at Northern California PET Imaging Center, Tesar and other PET advocates have high hopes for future applications and combinations of PET tracers that will allow doctors to create a more patient-specific health care plan, especially for brain imaging.

Currently, the radiologists there use FDG along with Amyvid, both distributed from Siemens’ PETNET, to create a more complete picture of a patient’s brain.

FDG scans show where glucose is in the brain and reveals patterns that indicate what kind of dementia the patient has. Tesar says the facility hasn’t decided whether FDG or Amyvid should go first in the diagnostic process, but that taken together, a physician can have a much clearer picture of the patient’s chance of having Alzheimer’s disease.

“From a health economics standpoint, it’s probably a tough pill to swallow, but clinically it really does help describe a much better picture for the patient,” she says.

Even if it takes some time for health care leaders to swallow the high cost of PET, overall, analysts expect PET to grow again after having experienced a slowdown, according to Millennium Research Group.

That means one of the industry’s newest tracers for neurology might have a chance to make its way into the market. A new tracer acquired by Eli Lilly from Siemens PETNET this April lights up tau, tangles in brain cells that indicate Alzheimer’s progression. It’s currently in phase zero, but Edgar Alvarez, director of global marketing for Siemens
PETNET solutions says the tracer could ultimately fit in well with an Alzheimer’s treatment plan.

Going forward, Siemens hopes its distribution of Amyvid and sodium fluoride tracers as well as other radiopharmaceuticals will help move focus on PET away from just FDG.

“The nice thing about Amyvid’s approval is that it shows PET goes beyond glucose metabolism, that it can provide additional clarities and different indications that weren’t necessarily thought of for PET,” says Alvarez. “Our initiative is to get awareness out in terms of what PET can offer.”