Glioma FMISO PET/MR Imaging Concurrent with Antiangiogenic Therapy: Molecular Imaging as a Clinical Tool in the Burgeoning Era of Personalized Medicine

Abstract

The purpose of this article is to provide a focused overview of the current use of positron emission tomography (PET) molecular imaging in the burgeoning era of personalized medicine in the treatment of patients with glioma. Specifically, we demonstrate the utility of PET imaging as a tool for personalized diagnosis and therapy by highlighting a case series of four patients with recurrent high grade glioma who underwent 18F-fluoromisonidazole (FMISO) PET/MR (magnetic resonance) imaging through the course of antiangiogenic therapy. Three distinct features were observed from this small cohort of patients. First, the presence of pseudoprogression was retrospectively associated with the absence of hypoxia. Second, a subgroup of patients with recurrent high grade glioma undergoing bevacizumab therapy demonstrated disease progression characterized by an enlarging nonenhancing mass with newly developed reduced diffusion, lack of hypoxia, and preserved cerebral blood volume. Finally, a reduction in hypoxic volume was observed concurrent with therapy in all patients with recurrent tumor, and markedly so in two patients that developed a nonenhancing reduced diffusion mass. This case series demonstrates how medical imaging has the potential to influence personalized medicine in several key aspects, especially involving molecular PET imaging for personalized diagnosis, patient specific disease prognosis, and therapeutic monitoring.

Radiation Necrosis, Pseudoprogression, Pseudoresponse, and Tumor Recurrence: Imaging Challenges for the Evaluation of Treated Gliomas

“…Other PET radiopharmaceuticals that are under investigation to differentiate between progression from pseudoprogression or tumor recurrence include 18 F-fluoromisonidazole (FMISO) PET/MR [48], 4-borono-2-[(18)F]-fluoro-phenylalanine ( 18 F-FBPA) PET [49], [(18)F]-fluoromethyl-dimethyl-2-hydroxyethylammonium ( 18 F-fluoromethylcholine) PET [50], and 3′-deoxy-3′-(18)F-fluorothymidine (FLT) PET [51].…”

Resolution of Spatial and Temporal Heterogeneity in Bevacizumab-Treated Breast Tumors by Eigenspectra Multispectral Optoacoustic Tomography

“…Accordingly, several preclinical studies in animal tumors documented elevations in tumor oxygenation (16,(29)(30)(31), whereas others reported increased intratumoral hypoxia (32)(33)(34) after the first few days of treatment with bevacizumab. The results from clinical studies in glioblastoma and breast cancer patients receiving bevacizumab therapy are equally contradictory, with some studies describing improvements in tumor oxygenation based on [ 18 F]fluoromisonidazole (FMISO) PET (35,36) or histology (37,38), and others reporting increases in intratumoral hypoxia based on FMISO uptake and/or diffuse optical spectroscopic imaging (DOSI) (39,40) and dynamic susceptibility contrast MRI (DSC-MRI) (41). Given the ability of eMSOT to provide accurate oxygenation readings at high spatiotemporal resolution and increased imaging depths, we hypothesized that longitudinal eMSOT imaging would offer valuable insights into the dynamics and spatial distribution of breast tumor oxygenation along the course of bevacizumab therapy.…”

Current Landscape and Emerging Fields of PET Imaging in Patients with Brain Tumors

“…More recently, [ 18 F]FMISO PET has been used for monitoring the effects of antiangiogenic therapy with bevacizumab in patients with recurrent malignant glioma [132,133]. It was shown that patients who had a response in both contrast-enhanced MRI and [ 18 F]FMISO PET had significantly longer survival than patients who responded on MRI only [133].…”