Brain's receptors sensitive to pot may 'open door' in treating drug dependence, brain disorders

Johns Hopkins scientists develop new PET radiotracer to visualize cannabinoid receptors, according to study released during SNM's 53rd Annual Meeting June 3–7 in San Diego

SAN DIEGO, Calif.--A team of Johns Hopkins researchers developed a new radiotracer--a radioactive substance that can be traced in the body--to visualize and quantify the brain's cannabinoid receptors by positron emission tomography (PET), opening a door to the development of new medications to treat drug dependence, obesity, depression, schizophrenia, Parkinson's disease and Tourette syndrome.

Discovery of the [11C]JHU75528 radioligand, a radioactive biochemical substance that is used to study the receptor systems of the brain, "opens an avenue for noninvasive study of central cannabinoid (CB1) receptors in the human and animal brain," explained Andrew Horti, assistant professor of radiology at Johns Hopkins Medicine, Baltimore, Md. He explained that there is evidence that CB1 receptors play an essential role in many disorders including schizophrenia, depression and motor function disorders. "Quantitative imaging of the central CB1 using PET could provide a great opportunity for the development of cannabinergic medications and for studying the role of CB1 in these disorders," added the co-author of "PET Imaging of Cerebral Cannabinoid CB1 Receptors with [11C]JHU75528."

Cannabinoid receptors are proteins on the surface of brain cells; they are most dense in brain regions involved with thinking and memory, attention and control of movement. The effects of tetrahydrocannabinol (THC), the primary psychoactive compound in marijuana, are due to its binding to specific cannabinoid receptors located on the surface of brain cells. "Blocking CB1 receptors presents the possibility of developing new, emerging medications for treatment of obesity and drug dependence including alcoholism, tobacco and marijuana smoking," said Horti.

The usefulness of in vivo (in the body) radioligands for studying cerebral receptors by PET depends on the image quality, and a good PET radiotracer must display a high level of specific receptor binding and low non-specific binding (binding with other proteins, cell membranes, etc.), said Horti. "If the non-specific binding is too high and specific binding is too low, the PET images become too 'noisy' for quantitative measurements," he noted. "We developed a PET radiotracer with a unique combination of good CB1 binding affinity and relatively low non-specific binding in mice and baboon brains," he added. "Previously developed PET radioligands for imaging of CB1 receptors were not suitable for quantitative imaging due to the high level of image 'noise,'" he added.

"Even though PET methodology was developed 30 years ago, its application for studying cerebral receptors is limited due to the lack of suitable radioligands," said Horti. "Development of [11C]JHU75528 will allow noninvasive research of CB1 receptor," he added, indicating that Johns Hopkins researchers need to complete various safety studies and obtain Food and Drug Administration approval before [11C]JHU75528 can be used for PET imaging in people.

"This discovery would not have been possible without involvement of many highly qualified researchers, including the teams of Robert Dannals and Dean Wong and support of Richard Wahl, director of the nuclear medicine department," said Horti.

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Abstract: A.G. Horti, H. Fan, H.T. Ravert, J. Hilton, A. Kumar, M. Alexander, A. Rahmim, H. Kuwabara, D.F. Wong and R.F. Dannals; Radiology, Johns Hopkins Medicine, Baltimore, Md., "PET Imaging of Cerebral Cannabinoid CB1 Receptors With [11C]JHU75528, SNM's 53rd Annual Meeting June 3–7, Scientific Paper 387.

About SNM

SNM is holding its 53rd Annual Meeting June 3–7 at the San Diego Convention Center. Research topics for the 2006 meeting include molecular imaging in clinical practice in the fight against cancer; the role of diagnostic imaging in the management of metastatic bone disease, metabolic imaging for heart disease, neuroendocrine and brain imaging, new agents for imaging infection and inflammation, and an examination of dementia, neurodegeneration, movement disorders and thyroid cancer.

SNM is an international scientific and professional organization of more than 16,000 members dedicated to promoting the science, technology and practical applications of molecular and nuclear imaging to diagnose, manage and treat diseases in women, men and children. Founded more than 50 years ago, SNM continues to provide essential resources for health care practitioners and patients; publish the most prominent peer-reviewed resource in the field; sponsor research grants, fellowships and awards; host the premier annual meeting for medical imaging; and train physicians, technologists, scientists, physicists, chemists and radiopharmacists in state-of-the-art imaging procedures and advances. SNM members have introduced--and continue to explore--biological and technological innovations in medicine that noninvasively investigate the molecular basis of diseases, benefiting countless generations of patients. SNM is based in Reston, Va.; additional information can be found online at http://www.snm.org.


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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