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Detection of Amyloid Plaques

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
85219
Program Year/Program:
2007 / SBIR
Agency Tracking Number:
AG024717
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
Molecular Neuroimaging, L.l.c.
60 TEMPLE STREET, SUITE 8A NEW HAVEN, CT -
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2007
Title: Detection of Amyloid Plaques
Agency: HHS
Contract: 1R43AG024717-01A2
Award Amount: $499,897.00
 

Abstract:

DESCRIPTION (provided by applicant): The goal of this research project is to define the structure and radioactive label for ligands that will per-mit quantitative measurement of amyloid sites in living brain by external imaging with positron (PET) or singl e photon (SPECT) emission tomography. A radiotracer that bound specifically to amyloid would be of great utility in diagnosis, monitoring treatment, and research of such Alzheimer's disease and related gerontological disorders. Based on preliminary in vitr o binding results using a classical structure-activity relationship approach, we found that certain benzoxazole derivatives showed affinity to amyloid protein in the nanomolar range. In this application we propose to test the following hypotheses: 1) Novel Indole and benzimidazole derivatives with appropriately functionalized aromatic substituents will favor binding to amyloid Ab(1-40) protein; and 2) radio-labeling with PET or SPECT radionuclides will provide a molecular probe that can image amyloid protei n in vivo. Specifically, this project poses the following specific aims AIM #1. Measure binding to amyloid protein of a group of benzothiazole derivatives already synthesized to expand the structure-activity relationship in this class of compounds. Nine ca ndidates will be tested by in vitro homogenate displacement binding against radiolabeled ligand for amyloid protein. AIM #2. Synthesize a defined library of halogenated heterocyclic analogs and screen for binding to amyloid protein. The working hypothesis is that the successful structure will incorporate the elements of an electron-donating group on an aromatic ring (A) attached to an aromatic heterocyclic 5/6 ring system (B/C). Eleven candidates will be synthesized and tested by in vitro homogenate displac ement binding against radiolabeled ligand for amyloid protein. AIM #3. Radiolabel the best candidates with radioactive I-123 or F-18 and determine their in vivo uptake properties in nonhuman primates. The candidates with binding affinities better than 10 n M will be radiolabeled and their lipophilicity will be measured as the octanol-buffer partition coefficient (log D). Compounds with log D less than 3.5 will be studied by dynamic regional brain imaging in nonhuman primates by with SPECT or PET. We estimate that four compounds per year will be imaged. The causes of Alzheimer's disease (AD) are still unclear, but postmortem examination of patient's brains reveal abundant senile plaques composed of amyloid-beta (Aa) peptides and neurofibrillary tangles formed by filaments of highly phosphorylated tau protein. Thus, a radiotracer that bound specifically to Aa protein would provide an in vivo measure of this process and would find application in the study, diagnosis, and treatment of psychiatric disorders. In thi s application we proposed to develop a selective compound to quantify these plaques in human.

Principal Investigator:

Gilles D. Tamagnan
2034014309
GTAMAGNAN@INDD.ORG

Business Contact:

Jack Mariotti
jmariotti@indd.org
Small Business Information at Submission:

MOLECULAR NEUROIMAGING, LLC
MOLECULAR NEUROIMAGING, LLC 60 TEMPLE STREET, SUITE 8A NEW HAVEN, CT 06510

EIN/Tax ID: 061594851
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No