https://www.selleckchem.com/products/sd-208.html PURPOSE GDC-0084 is an oral, brain-penetrant small molecule inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR). Since these two targets alter tumor vascularity and metabolism, respectively, we hypothesized multi-parametric MR-PET could be used to quantify the response, estimate pharmacokinetic (PK) parameters, and predict progression-free survival (PFS) in patients with recurrent malignant gliomas. EXPERIMENTAL DESIGN Multiparametric advanced MR-PET imaging was performed to evaluate physiological response in a first-in-man, multicenter, phase I, dose-escalation study of GDC-0084 (NCT01547546) in 47 patients with recurrent malignant glioma. RESULTS Measured maximum concentration (Cmax ) was associated with a decrease in enhancing tumor volume (P=0.0287) and an increase in fractional anisotropy (FA) (P=0.0418). Post-treatment tumor volume, 18F-FDG uptake, Ktrans, and relative cerebral blood volume (rCBV) were all correlated with Cmax A linear combination of change in 18F-FDG PET uptake, apparent diffusion coefficient (ADC), FA, Ktrans, vp, and rCBV were able to estimate both Cmax (R2=0.4113, P 1.25 uM*hr demonstrated significantly longer PFS compared with patients with a lower estimated concentration and exposure (P=0.0039 and P=0.0296, respectively). CONCLUSION Results from the current study suggest composite biomarkers created from multi-parametric MR-PET imaging targeting metabolic and/or physiologic processes specific to the drug mechanism of action may be useful for subsequent evaluation of treatment efficacy for larger phase II-III studies. Copyright ©2020, American Association for Cancer Research.Optic pathway gliomas are commonly associated with vision loss in children. We describe an 18-year-old woman with neurofibromatosis, type 1 and an optic nerve glioma who showed reproducible visual field defects that worsened midmenstrual cycle and returned to baseline during menses. To