New Fluorescence-Based Technology Allows Visualization of Cellular Activity of Molecular Imaging Pharmaceutical Candidates
New SAACQ Molecule May Advance R&D Productivity
Cambridge, MA, July 21, 2004 – Collaborative research conducted at McMaster University, Syracuse University and Molecular Insight Pharmaceuticals, Inc. demonstrates the expansion of the company’s Single Amino Acid Chelate (SAAC™) technology for use with fluorescent microscopy. The new fluorescence-based technology called SAACQ™ enables the visualization of radiopharmaceuticals interacting with cellular structures. This advance promises to accelerate the development of molecular imaging pharmaceuticals and targeted radiotherapeutics. The results were published in today’s Journal of the American Chemical Society (JACS).
"The ability to observe and monitor radiopharmaceuticals at the cellular and sub-cellular levels has previously not been possible," said Dr. John Valliant, Assistant Professor of Chemistry of McMaster University. "The opportunity to use fluorescent microscopy should increase R&D productivity by illuminating the mechanisms underlying the targeting of radiopharmaceuticals to specific molecular receptors."
The value of the SAACQ in drug discovery is its ability to precisely mimic the structure of a potential imaging pharmaceutical or targeted radiotherapeutic at the cellular level. It can also be applied to screening new pharmaceutical candidates including bioactive peptides and small molecules.
The SAACQ molecule is an analog of Molecular Insight’s SAAC technology designed for the stable attachment of metal radionuclides into peptides and proteins. The new molecular structure was created by incorporating quinolines in the metal binding portion of the molecule. This modification enhances the intensity of fluorescence of the SAAC molecule when non-radioactive rhenium is added, allowing live cell activity to be viewed by fluorescent microscopy. Previously, a fluorescent dye would be attached to a compound being studied to visualize cellular behavior, but the modification alters the behavior of the studied molecule, significantly diminishing the quality of the results. SAACQ allows the study of the original structure without modification.
"SAACQ helps bridge the gap between research in isolated cells and research in live subjects," said John Babich, Ph.D., President and Chief Scientific Officer of Molecular Insight. "Through SAACQ, we will better understand cellular behavior which will lead to the development of a new generation of molecular imaging pharmaceuticals and targeted radiotherapeutics with enhanced radiochemical stability."
Study Objectives
The study reported in JACS was designed to demonstrate that: (1) the rhenium complex of SAACQ has appropriate fluorescent properties to be used for in vitro microscopy studies; (2) the SAACQ ligand and its rhenium complex can be easily incorporated into peptides using a conventional automated synthesizer; and (3) the same SAACQ ligand can be labeled with the imaging radionuclide technetium-99m in high yield and the resulting complex be sufficiently robust for in vivo applications.
SAAC Technology
SAAC (Single Amino Acid Chelate) is Molecular Insight’s proprietary metal binding chemistry platform technology. It represents a new family of bifunctional chelates with superior binding of leading radioisotopes technetium and rhenium. This technology incorporates a metal binding (chelating) group into a single amino acid construct that can rapidly and efficiently bind to medically useful radionuclides for diagnostic and therapeutic uses. The amino acid portion of SAAC allows it to be inserted synthetically into any peptides sequence using conventional peptide chemistry.
SAAC can also be applied to peptides and proteins to create novel radiolabeled targeting agents for many diseases. In disease diagnosis and management, the improved radiolabel stability offered by SAAC allows for the sharper and more accurate delineation of disease through markedly improved images. Therapeutics based on this technology should be able to show high tumor uptake with less radiation exposure to healthy tissue. This enhanced specificity and potency may potentially increase efficacy and lower toxicity in the treatment of human disease.
In June, Molecular Insight and the University of Maryland reported on collaborative research demonstrating the potential of a molecule developed at the university incorporating SAAC technology to target angiogenesis in prostate cancer interchangeably with technetium-99m for diagnosis and rhenium-188 for therapy. The results were presented at the 2004 annual meeting of the Society of Nuclear Medicine.
About Molecular Insight Pharmaceuticals, Inc.
Molecular Insight Pharmaceuticals, Inc. is a privately held biopharmaceutical company focused on leveraging its proprietary technology platforms in molecular medicine to develop innovative pharmaceuticals to diagnose and treat disease. These products are designed to improve the management of disease by targeting, visualizing, treating and monitoring disease at the molecular level. The company, based in Cambridge, Massachusetts, has established a strong pipeline of molecular imaging candidates focused on the large and growing markets in cardiology, oncology and neurology. Molecular Insight is also applying its platform technologies to develop targeted radiotherapeutics for the treatment of cancer.
Contact:
Priscilla Harlan
Vice President, Corporate Communications
Molecular Insight Pharmaceuticals, Inc.
(617) 492-5554