MRI-Monitored Delivery of Sorafenib-Eluting Microspheres to Liver Tumors

Project: Research project

Description

Sorafenib is a potent multi-kinase inhibitor for the treatment of patients with unresectable hepatocellular
carcinoma (HCC). However, systemic exposures can lead to severe toxicities. Sorafenib dose often must be
reduced or administration discontinued altogether. Microsphere drug delivery platforms offer the potential to
significantly increase the efficacy of sorafenib therapy for HCC while reducing systemic exposures via targeted
image-guided transcatheter delivery. Quantitative approaches for imaging sorafenib-eluting microsphere
delivery may be critical to permit early prediction of response thus prompting adjustments to treatment
regimens as needed (additional infusions or adoption of alternative therapies). During this pre-clinical project
we seek to develop a powerful new approach for image-guided catheter-directed delivery of sorafenib to liver
tumors. We will address the following Specific Aims in a well-established VX-2 rabbit model of liver cancer:
Aim 1: Characterize the relationship between poly(D,L-lactide-co-glycolide) (PLG) microsphere fabrication
methods, sorafenib and contrast agent loading, size distribution, release kinetics, and MRI properties.
Aim 2: Optimize methods for in vivo MRI of SPIO-labeled sorafenib-eluting PLG microspheres and validate that
these methods permit accurate quantification of transcatheter delivery to liver tumors.
Aim 3: Validate that sorafenib-eluting microspheres inhibit angiogenesis and tumor growth, compare outcomes
in liver tumors treated with sorafenib-eluting microspheres, bland embolization, and sorafenib chemoembolization
(drug infusion without microsphere encapsulation), and finally compare MRI measurements of
transcatheter microsphere delivery to the elicited therapeutic responses.
StatusActive
Effective start/end date1/1/1512/31/19

Funding

  • National Cancer Institute (5R01CA181658-04 REVISED)

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Microspheres
Liver
Neoplasms
sorafenib
Liver Neoplasms
Complementary Therapies
Pharmaceutical Preparations
Contrast Media
Phosphotransferases
Therapeutics
Catheters
Rabbits
Growth