The overall goal of this collaborative Fast-Track project is clinical development of a novel 18F PET tracer for molecular imaging of receptors for vascular endothelial growth factor (VEGFR). This receptor is the major anti-angiogenic drug target in oncology patients. Critically, VEGFR prevalence decreases when VEGF/VEGFR anti-angiogenic inhibitors "work", and increases when these drugs stop "working". These findings provide a rationale for VEGFR imaging for image-guided anti-angiogenic therapy. To provide for high selectivity, specificity, and VEGFR-mediated intracellular accumulation, the 18F PET tracer will be targeted by VEGFR ligand, scVEGF. The protein will be site-specifically derivatized with a strained alkyne for copper-free click- chemistry radiolabeling with 18F-PEG(4)-azide. In Phase I of this project we will select the lead scVEGF/Alkyne conjugate, optimize conditions for 18F radiolabeling, and validate the use of lead tracer for monitoring anti- angiogenic therapy in a murine model of triple negative breast cancer. In Phase II we will produce cGMP grade conjugate, undertake FDA-required toxicology and dosimetry studies, and proceed to Phase I clinical trials in healthy volunteers.

Public Health Relevance

We propose to develop a novel, first-in-class 18F PET tracer for molecular imaging of receptors for vascular endothelial growth factor, which are the major drug targets in tumor neovasculature. The Fast-Track project involves preclinical development of click-chemistry 18F radiolabeling of a novel protein-based conjugate, cGMP production, pre-clinical toxicology/dosimetry, and Phase I clinical trials in healthy volunteers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
1R44CA177247-01A1
Application #
8648418
Study Section
Special Emphasis Panel (ZRG1-SBIB-T (10))
Program Officer
Zhao, Ming
Project Start
2014-09-16
Project End
2015-02-28
Budget Start
2014-09-16
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$222,920
Indirect Cost
Name
Sibtech, Inc.
Department
Type
DUNS #
966566465
City
Brookfield
State
CT
Country
United States
Zip Code
06804