Annotating MYC status with 89Zr-transferrin imaging

Nat Med. 2012 Oct;18(10):1586-91. doi: 10.1038/nm.2935. Epub 2012 Sep 23.

Abstract

A noninvasive technology that quantitatively measures the activity of oncogenic signaling pathways could have a broad impact on cancer diagnosis and treatment with targeted therapies. Here we describe the development of (89)Zr-desferrioxamine-labeled transferrin ((89)Zr-transferrin), a new positron emission tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71) with high avidity. The use of (89)Zr-transferrin produces high-contrast PET images that quantitatively reflect treatment-induced changes in MYC-regulated TFRC expression in a MYC-driven prostate cancer xenograft model. Moreover, (89)Zr-transferrin imaging can detect the in situ development of prostate cancer in a transgenic MYC prostate cancer model, as well as in prostatic intraepithelial neoplasia (PIN) before histological or anatomic evidence of invasive cancer. These preclinical data establish (89)Zr-transferrin as a sensitive tool for noninvasive measurement of oncogene-driven TFRC expression in prostate and potentially other cancers, with prospective near-term clinical application.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Deferoxamine
  • Male
  • Mice
  • Mice, Transgenic
  • Positron-Emission Tomography / methods*
  • Prostatic Intraepithelial Neoplasia / diagnostic imaging*
  • Prostatic Neoplasms / diagnostic imaging*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Radioisotopes
  • Radiopharmaceuticals
  • Receptors, Transferrin / metabolism
  • Transferrin*
  • Transplantation, Heterologous
  • Zirconium*

Substances

  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • Radioisotopes
  • Radiopharmaceuticals
  • Receptors, Transferrin
  • Tfrc protein, mouse
  • Transferrin
  • Zirconium
  • Deferoxamine