MILLIKELVIN TECHNOLOGIES, LLC — Department of Health and Human Services SBIR Phase I: NIA

Description

Project Summary Amyloid targeting radioactive PET agents have revolutionized screening of Alzheimer s Disease AD patients Amyloid PET agents e g florbetapir have enabled definitive rule out of the disease and patient selection for the testing of anti amyloid therapies However PET requires administration of a radioactive tracer An MRI based agent would enable lower cost more accessible and safer imaging for screening and longitudinal therapeutic monitoring Recently a low toxicity nanoparticle molecular imaging agent named ADx designed for MR imaging of amyloid plaque has been developed The ADx nanoparticle is a liposome containing targeting ligands and a high density of gadolinium Gd The ligands bind to A fibrils associated with amyloid plaque in the brain while the role of the Gd is to enhance MR image contrast between protons located in tissue near the ADx and those located farther away in the body ADx is a promising molecular MR imaging agent that can be used to image amyloid plaques in the brain without subjecting the patient to a radioactive burden Work to date on ADx imaging of amyloid plaques has all been conducted at Tesla This is because the nanoparticle like many Gd liposomal structures is most effective at producing image contrast at relatively low field This has hampered research on the nanoparticle because most clinical machines operate at higher fields of Tesla to Tesla unless addressed it will also impact potential translation to humans The present proposal exploits accelerated radiation damping ARD using driven feedback to improve imaging of a Gd liposomal agent such as ADx Under such conditions the magnetization vector of the protons is rotated back towards or away from equilibrium at a rate that is under operator control The degree of change in the proton magnetization vector depends on the linewidth of the protons The ADx nanoparticle produces strong local changes in proton linewidth Hence protons near the nanoparticle ie near the amyloid plaque to which the nanoparticle is bound will have much less of their magnetization vector changed as a result of establishing ARD conditions This will produce strong contrast between them and protons in the body located farther away This will be the first application of feedback driven ARD to improve image contrast on a molecular targeting agent Significantly in the MKT approach feedback driven contrast is complementary not competitive to any T weighting also used to provide contrast Thus it will serve to amplify existing T contrast produced by the ADx nanoparticle Project Narrative Amyloid PET agents e g florbetapir have revolutionized screening of Alzheimer s Disease AD but require subjecting patients to substantial ionizing radiation A non radioactive MRI agent called ADx has recently been developed and shown to target amyloid plaques but use of the agent is hampered because its effectiveness as a contrast agent declines at clinical MR field strengths MKT has developed a method of improving MR image contrast that will amplify existing contrast techniques so as to permit ADx and similar agents to produce the best possible in vivo images under clinical MR conditions