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NIH Research Festival

September 14 – 16, 2016

Theranostic Application of Radiolabeled Evans Blue-RGD Peptide Conjugate

Wednesday, September 14, 2016 – Poster Session I
3:00 – 4:30 p.m.

FAES Terrace

NIBIB

PHARM-1

Authors

  • O Jacobson
  • H Chen
  • J Zhang
  • G Niu
  • ID Weiss
  • DO Kiesewetter
  • Y Liu
  • Y Ma
  • F Li
  • H Wu
  • X Chen

Abstract

Objectives: One of the major design considerations for a drug is its pharmacokinetics in the blood. A drug with short half-life in the blood is less available at a target organ. Such a limitation dictates treatment with either high doses or more frequent doses, both of which may increase the likelihood of undesirable side effects. To address the need for additional methods to improve the blood half-life of drugs, we developed an “add-on” molecule that contains truncated Evans blue (EB) dye molecule that binds to albumin with moderate affinity and provides prolonged half-life in the blood; a metal chelate that allows radiolabeling for imaging and radiotherapy; and a maleimide for easy conjugation to drug molecules. Material and methods: The truncated EB was conjugated with NOTA or DOTA chelator and were denoted as NMEB and DMEB, respectively. As a proof-of-concept, we coupled NMEB or DMEB to c(RGDfK) for targeting integrin vß3. NMEB or DMEB were radiolabeled with Cu-64 or Y-90 respectively and tested in mice and in a human glioblastoma patient. Results: The resulting radiolabeled conjugates showed prolonged circulation half-life and enhanced tumor accumulation in αvβ3-expressing tumors. In a human patient with glioblastoma, our tracer accumulated in the tumor with high tumor-to-background ratio. Tumor radiotherapy experiments in mice using 90Y-DMEB-RGD showed promising results and eliminated existing tumors. Conclusions: Conjugation of our novel “add-on” molecules, NMEB or DMEB, to potential tracers and/or therapeutic agents improves blood half-life and tumor uptake, and can transform such agents into theranostic entities.

Scientific Focus Area: Molecular Pharmacology

This page was last updated on Friday, March 26, 2021

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2016 program

Download the 2016 Research Festival Schedule Overview (6 pages)

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