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A NOVEL VMAT 2 RADIOLIGAND FOR IMAGING PARKINSON'S

Award Number: R43MH068949
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/18/2003
PERIOD OF PERFORMANCE END DATE: 08/31/2005

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A NOVEL VMAT 2 RADIOLIGAND FOR IMAGING PARKINSON'S - DESCRIPTION (provided by applicant): Parkinson's disease (PD) is clinically characterized by bradykinesia, rigidity, tremor, and gait disturbance that progresses slowly over many years. The pathophysiological loss of dopamine neurons is a hallmark of this disorder and has guided treatments for reducing symptoms. Post mortem studies in PD demonstrate a marked reduction of dopamine neurons and the molecular targets located on terminals of dying neurons. These targets include the dopamine transporter (DAT) and vesicular monoamine transporters type 2 (VMAT 2). These two targets have been implicated in mediating the progression of the neurodegenerative process in PD. Neuroimaging techniques using positron emission tomography (PET) and single photon emission tomography (SPECT) have been useful in better characterizing the disease process in vivo in PD using these markers of dopamine cell loss. One presynaptic cell marker for VMAT 2 is l lc labeled tetrabenazine. This tracer has been used in a limited number of PD patients owing to the logistical difficulty in performing large-scale clinical evaluations. The widespread use and commercial application of the tracer is limited by the very short half-life of the l lc nuclide (20 rain) used to tag the chemical moiety. The wider use of this promising clinical and research tool will require a more practical radioisotope. In this application, we propose to develop a longer half-life (123I, half life 13 h) SPECT radiotracer for VMAT 2 imaging in PD patients. Our goal is to prepare a radioiodinated tetrabenazine analog. A simple radiochemical synthesis will be developed for this tracer. We will assess the in vitro properties of newly developed compounds. In addition, we will assess its biological properties in vivo using rodents that will include selectivity for the target site, penetrance in brain tissue, pharmacodynamic properties of the radioligand during pharmacological interventions in mice.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2004 ( Subtotal = $250,000 )
2004	2004	MOLECULAR NEUROIMAGING LLC	60 TEMPLE STREET	NEW HAVEN	CT	06510	SOUTH CENTRAL CT	USA	Mental Health Research Grants	000	2	8/6/2004	NON-COMPETING CONTINUATION	$250,000
														Subtotal = $250,000

Issue Date FY: 2003 ( Subtotal = $250,000 )
2003	2003	MOLECULAR NEUROIMAGING LLC	60 TEMPLE STREET	NEW HAVEN	CT	06510	SOUTH CENTRAL CT	USA	Mental Health Research Grants	000	1	9/18/2003	NEW	$250,000
														Subtotal = $250,000

Grand Total All Awards = $500,000

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A NOVEL VMAT 2 RADIOLIGAND FOR IMAGING PARKINSON'S

Award Number: R43MH068949

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/18/2003

PERIOD OF PERFORMANCE END DATE: 08/31/2005

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