[18F]-fluoromisonidazole (FMISO) PET/MRI hypoxic fraction distinguishes neuroinflammatory pseudoprogression from recurrent glioblastoma in patients treated with pembrolizumab

Abstract

Response assessment after immunotherapy remains a major challenge in glioblastoma due to an expected increased incidence of pseudoprogression. Gadolinium enhanced magnetic resonance imaging is the standard for monitoring therapeutic response, however, is markedly limited in characterizing pseudoprogression. Given that hypoxia is an important defining feature of glioblastoma regrowth, we hypothesized that [ 18F]-fluoromisonidazole FMISO PET could provide an additional physiological measure for the diagnosis of immunotherapeutic failure. Six patients with newly diagnosed glioblastoma who had previously received maximal safe resection followed by Stupp protocol CRT concurrent with Pembrolizumab immunotherapy were recruited for FMISO PET and Gd-MRI at the time of presumed progression. The hypoxic fraction was defined as the ratio of hypoxic volume to T1-weighted gadolinium enhancing volume. Four patients diagnosed with pseudoprogression demonstrated a mean hypoxic fraction of 9.8 ± 10%. Two with recurrent tumor demonstrated a mean hypoxic fraction of 131 ± 66%. Our results, supported by histopathology, suggest that the non-invasive assessment of hypoxic fraction by FMISO PET/MRI is clinically feasible and may serve as a biologically specific metric of therapeutic failure.

Diagnostic accuracy of glioma pseudoprogression identification with positron emission tomography imaging: a systematic review and meta-analysis

“…Regarding the direction and prospect of future investigation, first, the diagnostic value of non- 18 F-FET radiotracers need to be proved in additional cohorts. Second, only a few preliminary studies have shown that the highest diagnostic accuracy would be achieved from the combination of advanced multiparameter MRI and PET imaging ( 9 , 12 , 34 , 36 , 64 ), and therefore future research should focus on the development and validation of such bimodal or multimodal diagnostic models ( 65 ). In addition, the kinetic parameters of dynamic PET imaging have demonstrated excellent performance in glioma grading ( 66 ) and prognosis evaluation ( 16 , 35 , 38 , 40 ).…”

Amino Acid Tracer PET MRI in Glioma Management: What a Neuroradiologist Needs to Know

“…52 Intratumoral hypoxia is associated with resistance to treatment and entails radiation to hypoxic subregions of tumors. [ 18 F] fluoromisonidazole, a nitroimidazole derivative that images viable hypoxic cells, a biomarker of glioblastoma that correlates with prolonged overall survival 53 and distinguishes pseudoprogression from recurrence in patients with HGGs treated with pembrolizumab 54 [ 18 F]-GE-180 (a novel TSPO ligand), is an imaging biomarker of tumor heterogeneity with improved binding affinity and a high TBR in glioblastoma. TSPO-PET can differentiate potentially aggressive forms of gliomas, graded according to the World Health Organization (WHO) classification, with a positive rate on PET of 100% among the HGGs.…”