Therapeutic MRI using Florinated Tracers

University of Utah Technology Commercialization Office
posted on 07/01/2010

• request more info 
•   
•  LICENSE ONLINE

Summary: The invention integrates imaging technology with drug delivery technology to form a new technology platform: Therapeutic MRI. Novel fluorinated (19F) imaging tracers known as 19FIT produce a MRI signal without tissue background interference and are proven safe and rapidly excreted in mice. The general structure of the 19FIT molecule is a water-soluble asymmetric fluorinated dendrimer. Conjugation of 19FIT to a drug molecule results in a prodrug with dual imaging and therapeutic functions. The concentration of 19FIT is directly proportional to the MRI signal intensity. This technology will enable physicians to ensure that individuals are receiving the appropriate delivered dose of therapeutic drug at each treatment stage, with the potential to have a significant impact on reducing therapeutic variability and mis-dosing of drugs. The UMB inventor is testing several applications of the technology, for one, developing a prodrug of 19FIT linked to capecitabine, which is approved for the treatment of colorectal and breast cancers.

Applications: Cancer chemotherapy is a delicate balance between response and toxicity: while underdosing undermines response to therapy, overdosing results in excessive toxicity. Underdosing may occur in over 30% of patients receiving standard chemotherapeutic regimens, and H. Gurney calculates from published data a 20% relative reduction in survival for patients with node-positive breast cancer if underdosed based on body surface area (Br. J. Ca. 2002; 86: 1297). One way to improve cancer chemotherapy is to optimize drug dose for each patient (i.e., dose individualization). A genotype-based approach may be utilized to stratify patients (for example, to identify which patients may respond); however, this approach is not quantitative and does not account for dynamic changes in each patient's status. Measuring the delivered dose of a drug by therapeutic MRI will allow for the first time a truly quantitative approach to reduce mortality associated with drug mis-dosing and enable more consistent and effective therapeutic outcome for all patients.

Advantages:
Novel composition of dendritic imaging agent linked to therapeutic drug

Enables non-invasive and quantitative measurement of drug concentration

Potential new tool for use in drug development and to enable personalized drug dosing adjustments to achieve effective therapy for all patients

State of Development: The inventor's lab has developed a robust synthetic method for the class of 19FIT molecules and demonstrated safety in an animal model. Efficacy tests will be conducted in the mouse with 19FIT linked to capecitabine, and the group will engineer and test other technology applications.

R and D Required: Further efficacy testing prior to clinical trials.

Licensing Potential: Utah seeks partners for licensing, clinical development, and/or sponsored research to advance this technology into the healthcare field.

Patent Status: Multiple PCT applications have been filed for this technology.

Related Publications:
"Fluorous mixture synthesis of asymmetric dendrimers." Jiang ZX, Yu YB. J Org Chem. 2010 Mar 19;75(6):2044-9.

"Symmetry-Guided Design and Fluorous Synthesis of a Stable and Rapidly Excreted Imaging Tracer for (19)F MRI." Jiang ZX, Liu X, Jeong, EK, and Yu YB. Angew Chem Int Ed Engl. 2009;48(26):4755-8.

"Delivered Dose: A Drug-centric Phenotype for Chemotherapy Dose Individualization." Yu YB. Pharm Res. 2009 Aug;26(8):1803-6.

"The Design and Synthesis of Highly Branched and Spherically Symmetric Fluorinated Oils and Amphiles." Jiang ZX and Yu YB. Tetrahedron. 2007 May 7;63(19):3982-3988.