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MRI with Protease-Sensing Contrast Agents

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
70802
Program Year/Program:
2004 / STTR
Agency Tracking Number:
RR020835
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
ALERION BIOMEDICAL, INC.
ALERION BIOMEDICAL, INC. 6370 NANCY RIDGE DR, STE 106 SAN DIEGO, CA 92121 0321
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2004
Title: MRI with Protease-Sensing Contrast Agents
Agency: HHS
Contract: 1R41RR020835-01A1
Award Amount: $522,426.00
 

Abstract:

DESCRIPTION (provided by applicant): The goal of this Phase I STTR project is to design, synthesize, and test a new class of biochemically activated magnetic resonance imaging (MRI) contrast agents to detect and monitor enzymatic activity in vivo. The proposal responds to the Program Announcement entitled "Systems and methods for small animal imaging". We base this work on the hypothesis that activation of MRI contrast agents by extracellular proteases represents a particularly promising strategy to detect and image biochemical processes relevant to cancer. This represents a multi-disciplinary effort that brings together expertise in cancer biology, chemistry, enzymology, and physics at industrial and academic institutions to achieve the stated goals; specifically, we propose to determine if tumor-associated matrix metalloproteinase (MMP) activity can be non-invasively imaged by MRI in preclinical models of human cancer. We will approach the generation and testing of reagents useful for MRI detection of protease targets in Phase I of the project with the following specific aims: 1) Design and produce a gadolinium-chelate MRI contrast agent (Proteolytic Contrast Agent, PCA) that has decreased aqueous solubility following MMP cleavage of the agent; 2) Characterize the pharmacodynamic properties of both uncleaved and protease-cleaved PCAs in the context of in vivo mouse models of cancer. The success of the Phase I project will be judged by the completion of two well-defined milestones: 1) Preparation of one or more Gd-based MRI contrast agents that exhibit in vitro at least a 10-fold decrease in aqueous solubility in response to proteolytic cleavage by MMP; and 2) Collection of MRI data in vivo demonstrating a statistical difference in the value of k(out), the efflux transfer rate from the tumor, between MMP-positive and MMP-negative tumors and/or relative to that measured with an uncleavable analog in at least one of two mouse models of human cancer, i.e., by demonstrating a measured difference in the temporal response of the MRI contrast referable to proteolytic cleavage of the PCA. The success of this project has the potential for improved non-invasive detection and evaluation of cancer in small animals and eventually in patients. It provides the basis for Phase II of the project, with the overall goal of developing a commercial PCA product or products to provide for non-invasive clinical assessment to benefit patients with cancer, as well as to advance the use of MRI for functional imaging in clinical practice.

Principal Investigator:

Lynn M. Matrisian
6153433413
LYNN.MATRISIAN@VANDERBILT.EDU

Business Contact:


8585582191
DBAKAN@METAPROBE.COM
Small Business Information at Submission:

ALERION BIOMEDICAL, INC.
ALERION BIOMEDICAL, INC. 6370 NANCY RIDGE DR, STE 106 SAN DIEGO, CA 92121

EIN/Tax ID: 860852254
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
VANDERBILT UNIVERSITY
Medical Center
Nashville, TN 37203
RI Type: Nonprofit college or university