Tools

Back to the Top

Series

Task Force Focuses on Tracing Brain Amyloid

( 2 Articles Available, 0 Articles Pending )

Online training for use of Amyvid, the first FDA-approved Aβ imaging ligand, is now up and running,even as a task force convened by the Society of Nuclear Medicine and the Alzheimer's Association scrambles to formulate some expert guidelines on how amyloid imaging technology should be used in the clinic.

Coming to a City Near You: Tracer to Picture Brain Amyloid

 Lilly is getting ready for prime time—and to cash in. Amyvid, the first FDA-approved Aβ imaging ligand, is now available to researchers within reach of 16 manufacturing sites across the United States, according to a June 1 press release by Eli Lilly and Company and Avid Radiopharmaceuticals, Inc. Online training for use of the ligand is now up and running, and in-person training began 11 June 2012, starting in Miami. Manufacturing, distribution, and the FDA-stipulated user training are gearing up, even as a task force convened by the Society of Nuclear Medicine and the Alzheimer's Association scrambles to formulate some expert guidelines on how amyloid imaging technology should be used in the clinic (see Part 2 of this series).

Amyvid—aka florbetapir—is the first to receive the agency’s nod among several imaging ligands that burst onto the clinical scene in the past eight years (see ARF related news story). Others include florbetaben from Piramal Healthcare, flutemetamol from GE Healthcare (see ARF related news story and ARF related update), and AZD4694 by AstraZeneca (see ARF related news story). These 18F-based ligands reveal amyloid plaques in positron emission tomography (PET) scans. The original compound, Pittsburgh Compound B (see ARF related news story), is widely used in research, but requires a nearby cyclotron because of its very short half-life.

States that manufacture the 18F-labeled compound at present include Arizona (Phoenix), California (Palo Alto, Colton), Connecticut (Hartford), Georgia (Atlanta), Florida (Fort Lauderdale, Orlando, Jacksonville), Illinois (Chicago), Missouri (St. Louis), North Carolina (Charlotte), Ohio (Columbus), Pennsylvania (North Wales), Texas (Dallas, Houston), and Washington (Seattle). With its half-life of 110 minutes, Amyvid must go directly to imaging centers from special radiopharmacies where it is produced. Imaging centers within a reasonable distance will be able to get the drug for now. (For instance, Boston centers will get their Amyvid from the Hartford center.) In the future, more sites will manufacture the compound.

An FDA advisory panel first rejected Amyvid back in January of 2011 (see ARF related news story) on the condition that Lilly improve the reliability among readers of the PET scans. In response, Lilly and Avid devised an online training program that takes some three hours. The company also teamed up with the American College of Radiology to train readers in person. A three- to five-hour program was launched in Miami on 11 June, with future sites to be announced later. Each program trains radiologists and nuclear medicine physicians who will read the PET scans. The company warns that physicians should not read the scans unless they have been trained; even then, some error may still occur when estimating plaque density, they say.

Amyvid's actual indication, as it appears on the product label, is "to estimate beta-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease (AD) and other causes of cognitive decline." But big insurers have not yet decided whether, and in what instances, they will cover the scan. For example, if all diagnostic signs point to AD, will they pay for the scan? Will they reimburse for those in whom an AD diagnosis is uncertain?

Insurers usually follow the lead of the Center for Medicare and Medicaid Services (CMS). "We are aware of Amyvid and are having internal discussions about it, but have nothing to share publicly just yet," said a representative of the U.S. federal agency, based in Baltimore, Maryland.

Amyvid and other amyloid PET ligands will best be used to diagnose patients who present with confusing symptoms of dementia, said Andrew Budson, Boston University. "With some patients, it is difficult to figure out whether they have Alzheimer's disease or another disorder," he said. A scan of a person with documented memory problems showing little to no plaque would rule out AD. On the other hand, a positive scan does not automatically mean AD is the only etiology, Budson said. For example, a subdural hematoma could cause additional cognitive impairment even in the presence of AD plaques, and amyloid plaques are found in people who appear cognitively normal (see ARF related news story). For that reason, primary care physicians especially must be aware that this scan should be used in conjunction with, not in lieu of, other tests already in use for AD, said Budson. He stressed that, given the lack of disease-modifying treatments and a dearth of data on whether or not normal people with amyloid later become demented, those without memory problems should not get this diagnostic at this time. Despite inquiries from a reporter, Lilly would not divulge how it plans to market Amyvid. The Society of Nuclear Medicine (SNM) and the Alzheimer's Association have set up a task force to develop guidelines for using this technology (see Part 2 of this series).—Gwyneth Dickey Zakaib.

This is Part 1 of a two-part series. See also Part 2.

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

News Citations

  1. Amyloid Imaging Task Force to Work Out Technology's Use
  2. FDA Approves Amyvid for Clinical Use
  3. Toronto: Last Gift to Science—Hospice Patients Validate Amyloid Ligand
  4. Miami: Updates on J-ADNI, 18F Tracers, Biopsies
  5. Geneva: The AstraZeneca Ligand—The Fairest of Them All?
  6. Pittsburgh Compound-B Zooms into View
  7. Committee Shoots Down Florbetapir, Raising Bar for Field at Large
  8. HAI Chicago: PIB in Healthy People

External Citations

  1. press release
  2. online training program

Further Reading

Papers

  1. Newberg AB, Arnold SE, Wintering N, Rovner BW, Alavi A. Initial clinical comparison of 18F-florbetapir and 18F-FDG PET in patients with Alzheimer disease and controls. J Nucl Med. 2012 Jun;53(6):902-7. PubMed.
  2. Villemagne VL, Mulligan RS, Pejoska S, Ong K, Jones G, O'Keefe G, Chan JG, Young K, Tochon-Danguy H, Masters CL, Rowe CC. Comparison of (11)C-PiB and (18)F-florbetaben for Aβ imaging in ageing and Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2012 Jun;39(6):983-9. PubMed.
  3. Fleisher AS, Chen K, Liu X, Ayutyanont N, Roontiva A, Thiyyagura P, Protas H, Joshi AD, Sabbagh M, Sadowsky CH, Sperling RA, Clark CM, Mintun MA, Pontecorvo MJ, Coleman RE, Doraiswamy PM, Johnson KA, Carpenter AP, Skovronsky DM, Reiman EM. Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease. Neurobiol Aging. 2012 May 24; PubMed.

Amyloid Imaging Task Force to Work Out Technology's Use

With amyloid plaque imaging poised to burst into clinical practice, could the technology be used inappropriately? The question is no longer academic. Amyvid, the F18-labeled tracer recently approved by the Food and Drug Administration (see ARF related news story), is already available for use from radiopharmacies at 16 sites across the U.S. (see Part 1 of this series). The Society of Nuclear Medicine and Molecular Imaging and the Alzheimer's Association have assembled a 14-member Amyloid Imaging Task Force to develop guidelines for, among others, radiologists, neurologists, and general practice physicians, who will use this technology most. The task force has been meeting since April of this year and plans to issue draft recommendations to the research community this July.

"Our objective is to try to form a recommendation as to how this technology should be used in clinical practice, and perhaps even in research," said task force member Maria Carrillo of the Alzheimer's Association, headquartered in Chicago. "We will try to come up with a list of recommendations not only for the healthcare community, but for family members who are wondering if their loved ones should get an amyloid imaging scan," she said.

The task force meets by conference call once every two weeks and will review more than 120 scientific publications on the clinical use of amyloid positron emission tomography (PET) tracers. The group wants to recommend when and why the scan should be used, since indications on the FDA label are relatively brief and only address safety and efficacy, said committee co-chair Satoshi Minoshima, a PET expert at the University of Washington, Seattle. The task force will go a step further and recommend what kind of patient may actually benefit from the technology. For now, and until there is a treatment to prevent or cure AD, the technology will not help everyone, he said.

"We are also looking beyond the published evidence to ask experts in the field what they think could be appropriate in circumstances about which there are no published evidence," said Keith Johnson, of Massachusetts General Hospital in Boston, also a co-chair of the committee. He was careful to point out that Amyvid is but the first of several plaque-imaging PET compounds that could be FDA approved in the near future. Others include florbetaben from Piramal Healthcare, flutemetamol from GE Healthcare (see ARF related update), and AZD4694 by AstraZeneca (see ARF related news story).

The group aims to present a draft at the Alzheimer's Association International Conference (AAIC) in 2012, to be held in Vancouver, Canada, said Carrillo. There, the scientific community will be able to offer feedback. When in its final form, at a date to be determined late in 2012, the guidelines will be published in the Association’s journal Alzheimer's and Dementia and on the SNM and Association websites, said Carrillo. They will appear in videos and educational materials that target families, caregivers, and the public at large.

The committee has reached no decisions yet, but Johnson already foresees a few broad areas of agreement. First, this technology is inappropriate for clinical use in cognitively normal people who, even if they have subjective memory complaints, have no formal evidence of cognitive impairment. On the other end of the spectrum, in Johnson’s view, the technology is inappropriate if there is little doubt that AD is present. If, however, there is substantial doubt about whether measurable impairment is due to AD, and when the information obtained would significantly alter medical management, then an amyloid PET scan could be useful. The full consensus of the committee will remain unknown until at least the AAIC conference. What's more, this task force will likely be the start of a longer process, said Johnson. There may be other efforts around the globe coming up with similar guidelines, and any policies will probably require revisiting as the literature on the topic evolves, Johnson said.

For now, Lilly is following the FDA-approved indication. "We applaud the Alzheimer's Association and Society of Nuclear Medicine's commitment to providing their members with guidance on this new technology," said a company representative. However, she added, "the Amyvid label contains guidance that is based on FDA-approved science and should always be the first resource for information on how, and in whom, to use Amyvid."

The FDA's label is not the be-all end-all of the matter, insists Minoshima. "FDA approval for the safety and efficacy of commercial tracers has to be carefully translated to [ensure the] appropriate use of the technology for the benefit of patients," he told Alzforum in an e-mail. The indication says nothing, for instance, about people who have subjective memory complaints or who are certain to have AD. "In this regard, careful considerations and discussions are necessary," said Minoshima. The other 12 members of the task force include seven academics: Nicolaas Bohnen, University of Ann Arbor, Michigan; Kevin Donohoe, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Norm Foster, University of Utah, Salt Lake City; Peter Herscovitch, National Institutes of Health, Bethesda, Maryland; Jason Karlawish, University of Pennsylvania, Philadelphia; Christopher Rowe, Austin Hospital, Melbourne, Australia; and William Klunk, University of Pittsburgh, Pennsylvania. Completing the panel are Kristi Mitchell and Virginia Papas from the Society of Nuclear Medicine and Molecular Imaging and three representatives from the Alzheimer’s Association, Bill Thies, Maria Carrillo, and Dean Hartley.—Gwyneth Dickey Zakaib.

This concludes a two-part series. See also Part 1.

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

News Citations

  1. FDA Approves Amyvid for Clinical Use
  2. Coming to a City Near You: Tracer to Picture Brain Amyloid
  3. Miami: Updates on J-ADNI, 18F Tracers, Biopsies
  4. Geneva: The AstraZeneca Ligand—The Fairest of Them All?

External Citations

  1. Alzheimer's and Dementia

Further Reading

Papers

  1. Ossenkoppele R, Zwan MD, Tolboom N, van Assema DM, Adriaanse SF, Kloet RW, Boellaard R, Windhorst AD, Barkhof F, Lammertsma AA, Scheltens P, van der Flier WM, van Berckel BN. Amyloid burden and metabolic function in early-onset Alzheimer's disease: parietal lobe involvement. Brain. 2012 Jul;135(Pt 7):2115-25. PubMed.
  2. Fodero-Tavoletti MT, Brockschnieder D, Villemagne VL, Martin L, Connor AR, Thiele A, Berndt M, McLean CA, Krause S, Rowe CC, Masters CL, Dinkelborg L, Dyrks T, Cappai R. In vitro characterization of [(18)F]-florbetaben, an Aβ imaging radiotracer. Nucl Med Biol. 2012 Apr 11; PubMed.
  3. Gelosa G, Brooks DJ. The prognostic value of amyloid imaging. Eur J Nucl Med Mol Imaging. 2012 Jul;39(7):1207-19. PubMed.
  4. Camus V, Payoux P, Barré L, Desgranges B, Voisin T, Tauber C, La Joie R, Tafani M, Hommet C, Chételat G, Mondon K, De la Sayette V, Cottier JP, Beaufils E, Ribeiro MJ, Gissot V, Vierron E, Vercouillie J, Vellas B, Eustache F, Guilloteau D. Using PET with (18)F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment. Eur J Nucl Med Mol Imaging. 2012 Apr;39(4):621-31. PubMed.