Imaging adult glioma with ⁶⁸Ga-citrate PET/MR

Objectives: ninvasive tools that selectively target tumor cells could improve the management of primary brain tumors. Cancer generally has a high demand for Fe(III), an essential nutrient for a variety of biochemical processes. We tested whether preclinical models and clinical high grade glioma can be detected with PET/MR using ⁶⁸Ga(IV), a Fe(III) biomimetic that binds to transferrin in blood. Preclinical animal studies showed that ⁶⁸Ga(IV) accumulated in U87MG, a model of high grade glioma, in a transferrin receptor-dependent fashion within 4 hours post injection. All normal tissues, including the brain, had comparatively lower radiotracer uptake, with the exception of bone. Subsequently, fourteen patients with WHO grade III or IV glioma received 3.7 - 10 mCi of ⁶⁸Ga-citrate and were imaged with PET/MR 102 - 303 minutes post injection. Multiple contrast-enhancing lesions were PET avid, while normal brain tissue was not. Several contrast-enhancing lesions were not PET avid, which suggests a receptor mediated mechanism of tumor uptake, rather than nonspecific accumulation in regions with aberrant vasculature. One minimally enhancing tumor and a tumor with significantly reduced enhancement post treatment with bevacizumab were PET avid. These early data demonstrate that high-grade glioma is detectable with a radiotracer targeted to its molecular characteristics. Further studies are being performed to establish the role of this novel imaging technique in the management of patients.