Avid Radiopharmaceuticals
Encyclopedia
Avid Radiopharmaceuticals is an American
company, founded by Dr. Daniel Skovronsky, and based at the University City Science Center
research campus in Philadelphia, Pennsylvania
. The company has developed a radioactive tracer
called 18F-AV-45. AV-45 can be used to detect beta amyloid plaques in patients with memory problems using positron emission tomography
(PET) scans, making the company the first to bring to market an FDA-approved method that can directly detect this hallmark pathology of Alzheimer's disease
.
Eli Lilly and Company
announced on November 8, 2010, that they would acquire Avid for $800 million, with $300 million paid out up front and the balance paid later on.
in 1906, the only certain way to determine if a person indeed had the disease was to perform an autopsy
on the patient's brain to find distinctive spots on the brain that show the buildup of amyloid plaque. Doctors must diagnose the disease in patients with memory loss and dementia
based on symptoms, and as many as 20% of patients diagnosed with the disease are found after examination of the brain following death to not have had the condition. Other diagnostic tools, such as analysis of cerebrospinal fluid
, magnetic resonance imaging
scans looking for brain shrinkage and PET scans looking at how glucose
was used in the brain, had all been unreliable.
Avid built on research done by Drs. William Klunk and Chester Mathis who had developed a substance they called Pittsburgh compound B
as a means of detecting amyloid plaque, after analyzing 400 prospective compounds and developing 300 variations of the substance that they had discovered might work. In 2002, a study performed in Sweden
on Alzheimer's patients was able to detect the plaque in PET brain scans. Later studies on a control group member without the disease did not find plaque, confirming the reliability of the compound in diagnosis. While the tool worked, Pittsburgh compound B relies on the use of carbon-11, a radioactive isotope with a half-life of 20 minutes that requires the immediate use of the material prepared in a cyclotron
.
Dr. Skovronsky established Avid Radiopharmaceuticals in July 2005 with the goal of finding a dye that could be injected into the body, would cross the blood-brain barrier
and attach itself to amyloid protein deposits in the brain. Avid raised $500,000 from BioAdvance, the Biotechnology Greenhouse of Southeastern Pennsylvania, as seed funding toward the development of a biological marker. Once they found a candidate dye, they attached the positron
-emitting fluorine-18
, a radioactive isotope
with a half-life
of nearly two hours that is used annually in two million PET scans and that can last for as long as a day when prepared in the morning by cyclotron. The dye had been developed and patented by the University of Pennsylvania
and was licensed by Avid.
Initial tests in 2007 on a patient at Johns Hopkins University Hospital previously diagnosed with symptoms of Alzheimer's disease detected plaque in a PET scan in areas where it was typically found in the brain. Further tests found that the scans detected plaque in patients with Alzheimer's, didn't find it in those without the diagnosis and found intermediate amounts in patients with early signs of dementia. The tests found amyloid plaque in 20% of its test patients over age 60 that had been in the normal range, but had performed worse than a control group on tests of mental acuity.
In order to confirm if the dye was accurate in detecting Alzheimer's, an advisory committee at the Food and Drug Administration
demanded that the team of Avid, Bayer
and General Electric
perform a study to test their method. Avid established a study with a group of 35 hospice
patients, some that had been diagnosed with dementia and others that had no memory problems. The participants and their families agreed that they would undergo the PET scans and would have their brains autopsied after their death by pathologists. After the study was conducted, Avid received confirmation in May 2010 that the results of the test were successful in distinguishing between those with Alzheimer's and those without the disease.
In results presented in July 2010 to an international conference on Alzheimer's disease held in Hawaii
, the company showed that for 34 out of the 35 hospice patients who had been scanned, the initial scan results were confirmed when pathologists counted plaque under a microscope and when a computerized scan of the plaque was performed on material from the autopsied brain. The findings will require review by the FDA to confirm its reliability as a means of diagnosing the disease. If confirmed, the technique would provide a means to reliably diagnose and monitor the progress of Alzheimer's and would allow potential pharmaceutical treatments to be evaluated.
In a study published in January 2011 in the Journal of the American Medical Association
, Avid reported on the results of further studies conducted based on 152 test subjects who had agreed to receive the company's PET scans and to have their brains analyzed after death for definitive determination of the presence of amyloid plaques. Of the patients included in the study, 29 who died had autopsies performed on their brains and in all but one the brain autopsy results matched the diagnosis based on the PET scan taken before death. Avid's technique is being used to test the efficacy of Alzheimer's disease treatments being developed by other pharmaceutical firms as a means of determining the ability of the drugs to reduce the buildup of amyloid protein in the brains of living subjects.
On January 20, 2011, an FDA advisory committee unanimously recommended that Avid's PET scan technique be approved for use. The advisory committee included a qualification requiring Avid to develop clear guidelines establishing when the tests had spotted enough of the amyloid plaque in order to make a diagnosis of Alzheimer's, a task that Avid CEO Dr. Daniel M. Skovronsky stated could be resolved in several months.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
company, founded by Dr. Daniel Skovronsky, and based at the University City Science Center
University City Science Center
The University City Science Center is the first and largest urban research park in the United States. It was established in 1963 with its headquarters in the University City neighborhood of Philadelphia...
research campus in Philadelphia, Pennsylvania
Pennsylvania
The Commonwealth of Pennsylvania is a U.S. state that is located in the Northeastern and Mid-Atlantic regions of the United States. The state borders Delaware and Maryland to the south, West Virginia to the southwest, Ohio to the west, New York and Ontario, Canada, to the north, and New Jersey to...
. The company has developed a radioactive tracer
Radioactive tracer
A radioactive tracer, also called a radioactive label, is a substance containing a radioisotope that is used to measure the speed of chemical processes and to track the movement of a substance through a natural system such as a cell or tissue...
called 18F-AV-45. AV-45 can be used to detect beta amyloid plaques in patients with memory problems using positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET) scans, making the company the first to bring to market an FDA-approved method that can directly detect this hallmark pathology of Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.
Eli Lilly and Company
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
announced on November 8, 2010, that they would acquire Avid for $800 million, with $300 million paid out up front and the balance paid later on.
Detection of Alzheimer's disease
Since the disease was first described by Dr. Alois AlzheimerAlois Alzheimer
Aloysius "Alois" Alzheimer, was a German psychiatrist and neuropathologist and a colleague of Emil Kraepelin. Alzheimer is credited with identifying the first published case of "presenile dementia", which Kraepelin would later identify as Alzheimer's disease....
in 1906, the only certain way to determine if a person indeed had the disease was to perform an autopsy
Autopsy
An autopsy—also known as a post-mortem examination, necropsy , autopsia cadaverum, or obduction—is a highly specialized surgical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present...
on the patient's brain to find distinctive spots on the brain that show the buildup of amyloid plaque. Doctors must diagnose the disease in patients with memory loss and dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
based on symptoms, and as many as 20% of patients diagnosed with the disease are found after examination of the brain following death to not have had the condition. Other diagnostic tools, such as analysis of cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
, magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
scans looking for brain shrinkage and PET scans looking at how glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
was used in the brain, had all been unreliable.
Avid built on research done by Drs. William Klunk and Chester Mathis who had developed a substance they called Pittsburgh compound B
Pittsburgh compound B
Pittsburgh compound B is a fluorescent analog of thioflavin T, which can be used in positron emission tomography scans to image beta-amyloid plaques in neuronal tissue...
as a means of detecting amyloid plaque, after analyzing 400 prospective compounds and developing 300 variations of the substance that they had discovered might work. In 2002, a study performed in Sweden
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
on Alzheimer's patients was able to detect the plaque in PET brain scans. Later studies on a control group member without the disease did not find plaque, confirming the reliability of the compound in diagnosis. While the tool worked, Pittsburgh compound B relies on the use of carbon-11, a radioactive isotope with a half-life of 20 minutes that requires the immediate use of the material prepared in a cyclotron
Cyclotron
In technology, a cyclotron is a type of particle accelerator. In physics, the cyclotron frequency or gyrofrequency is the frequency of a charged particle moving perpendicularly to the direction of a uniform magnetic field, i.e. a magnetic field of constant magnitude and direction...
.
Dr. Skovronsky established Avid Radiopharmaceuticals in July 2005 with the goal of finding a dye that could be injected into the body, would cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
and attach itself to amyloid protein deposits in the brain. Avid raised $500,000 from BioAdvance, the Biotechnology Greenhouse of Southeastern Pennsylvania, as seed funding toward the development of a biological marker. Once they found a candidate dye, they attached the positron
Positron
The positron or antielectron is the antiparticle or the antimatter counterpart of the electron. The positron has an electric charge of +1e, a spin of ½, and has the same mass as an electron...
-emitting fluorine-18
Fluorine-18
Fluorine-18 is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380 u and its half-life is 109.771 minutes....
, a radioactive isotope
Radionuclide
A radionuclide is an atom with an unstable nucleus, which is a nucleus characterized by excess energy available to be imparted either to a newly created radiation particle within the nucleus or to an atomic electron. The radionuclide, in this process, undergoes radioactive decay, and emits gamma...
with a half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
of nearly two hours that is used annually in two million PET scans and that can last for as long as a day when prepared in the morning by cyclotron. The dye had been developed and patented by the University of Pennsylvania
University of Pennsylvania
The University of Pennsylvania is a private, Ivy League university located in Philadelphia, Pennsylvania, United States. Penn is the fourth-oldest institution of higher education in the United States,Penn is the fourth-oldest using the founding dates claimed by each institution...
and was licensed by Avid.
Initial tests in 2007 on a patient at Johns Hopkins University Hospital previously diagnosed with symptoms of Alzheimer's disease detected plaque in a PET scan in areas where it was typically found in the brain. Further tests found that the scans detected plaque in patients with Alzheimer's, didn't find it in those without the diagnosis and found intermediate amounts in patients with early signs of dementia. The tests found amyloid plaque in 20% of its test patients over age 60 that had been in the normal range, but had performed worse than a control group on tests of mental acuity.
In order to confirm if the dye was accurate in detecting Alzheimer's, an advisory committee at the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
demanded that the team of Avid, Bayer
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...
and General Electric
General Electric
General Electric Company , or GE, is an American multinational conglomerate corporation incorporated in Schenectady, New York and headquartered in Fairfield, Connecticut, United States...
perform a study to test their method. Avid established a study with a group of 35 hospice
Hospice
Hospice is a type of care and a philosophy of care which focuses on the palliation of a terminally ill patient's symptoms.In the United States and Canada:*Gentiva Health Services, national provider of hospice and home health services...
patients, some that had been diagnosed with dementia and others that had no memory problems. The participants and their families agreed that they would undergo the PET scans and would have their brains autopsied after their death by pathologists. After the study was conducted, Avid received confirmation in May 2010 that the results of the test were successful in distinguishing between those with Alzheimer's and those without the disease.
In results presented in July 2010 to an international conference on Alzheimer's disease held in Hawaii
Hawaii
Hawaii is the newest of the 50 U.S. states , and is the only U.S. state made up entirely of islands. It is the northernmost island group in Polynesia, occupying most of an archipelago in the central Pacific Ocean, southwest of the continental United States, southeast of Japan, and northeast of...
, the company showed that for 34 out of the 35 hospice patients who had been scanned, the initial scan results were confirmed when pathologists counted plaque under a microscope and when a computerized scan of the plaque was performed on material from the autopsied brain. The findings will require review by the FDA to confirm its reliability as a means of diagnosing the disease. If confirmed, the technique would provide a means to reliably diagnose and monitor the progress of Alzheimer's and would allow potential pharmaceutical treatments to be evaluated.
In a study published in January 2011 in the Journal of the American Medical Association
Journal of the American Medical Association
The Journal of the American Medical Association is a weekly, peer-reviewed, medical journal, published by the American Medical Association. Beginning in July 2011, the editor in chief will be Howard C. Bauchner, vice chairman of pediatrics at Boston University’s School of Medicine, replacing ...
, Avid reported on the results of further studies conducted based on 152 test subjects who had agreed to receive the company's PET scans and to have their brains analyzed after death for definitive determination of the presence of amyloid plaques. Of the patients included in the study, 29 who died had autopsies performed on their brains and in all but one the brain autopsy results matched the diagnosis based on the PET scan taken before death. Avid's technique is being used to test the efficacy of Alzheimer's disease treatments being developed by other pharmaceutical firms as a means of determining the ability of the drugs to reduce the buildup of amyloid protein in the brains of living subjects.
On January 20, 2011, an FDA advisory committee unanimously recommended that Avid's PET scan technique be approved for use. The advisory committee included a qualification requiring Avid to develop clear guidelines establishing when the tests had spotted enough of the amyloid plaque in order to make a diagnosis of Alzheimer's, a task that Avid CEO Dr. Daniel M. Skovronsky stated could be resolved in several months.