title: Annotating MYC status with 89Zr-transferrin imaging.
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.
authors.affiliation: Radiochemistry Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Holland
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Evans
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Rice
authors.forename: John
authors.initials: J
authors.lastname: Wongvipat
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sawyers
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
mesh_terms: D000818:Animals; D003676:Deferoxamine; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography / Q000379:methods*; D019048:Prostatic Intraepithelial Neoplasia / Q000000981:diagnostic imaging*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin; D014183:Transplantation, Heterologous; D015040:Zirconium
chemical_list: C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse; D014168:Transferrin; D015040:Zirconium; D003676:Deferoxamine