Targeting iron metabolism in high-grade glioma with 68Ga-citrate PET/MR.

Autor: Behr SC; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Villanueva-Meyer JE; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Li Y; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Wang YH; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Wei J; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Moroz A; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA.; Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, Moscow, Russia., Lee JK; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Hsiao JC; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Gao KT; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Ma W; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Cha S; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Wilson DM; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Seo Y; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Nelson SJ; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA.; Helen Diller Family Comprehensive Cancer Center.; Department of Bioengineering and Therapeutic Sciences., Chang SM; Helen Diller Family Comprehensive Cancer Center.; Department of Neurological Surgery, and., Evans MJ; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA.; Helen Diller Family Comprehensive Cancer Center.; Department of Pharmaceutical Chemistry, UCSF, San Francisco, California, USA.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2018 Nov 02; Vol. 3 (21). Date of Electronic Publication: 2018 Nov 02.
DOI: 10.1172/jci.insight.93999
Abstrakt: Noninvasive tools that target tumor cells could improve the management of glioma. Cancer generally has a high demand for Fe(III), an essential nutrient for a variety of biochemical processes. We tested whether 68Ga-citrate, an Fe(III) biomimetic that binds to apo-transferrin in blood, detects glioma in preclinical models and patients using hybrid PET/MRI. Mouse PET/CT studies showed that 68Ga-citrate accumulates in subcutaneous U87MG xenografts in a transferrin receptor-dependent fashion within 4 hours after injection. Seventeen patients with WHO grade III or IV glioma received 3.7-10.2 mCi 68Ga-citrate and were imaged with PET/MR 123-307 minutes after injection to establish that the radiotracer can localize to human tumors. Multiple contrast-enhancing lesions were PET avid, and tumor to adjacent normal white matter ratios were consistently greater than 10:1. Several contrast-enhancing lesions were not PET avid. One minimally enhancing lesion and another tumor with significantly reduced enhancement following bevacizumab therapy were PET avid. Advanced MR imaging analysis of one patient with contrast-enhancing glioblastoma showed that metabolic hallmarks of viable tumor spatially overlaid with 68Ga-citrate accumulation. These early data underscore that high-grade glioma may be detectable with a radiotracer that targets Fe(III) transport.
Databáze: MEDLINE