{"doi":"10.7150/thno.47317","title":"MR-detectable metabolic biomarkers of response to mutant IDH inhibition in low-grade glioma","abstract":"Mutations in isocitrate dehydrogenase 1 (IDH1mut) are reported in 70-90% of low-grade gliomas and secondary glioblastomas. IDH1mut catalyzes the reduction of -ketoglutarate (-KG) to 2-hydroxyglutarate (2-HG), an oncometabolite which drives tumorigenesis. Inhibition of IDH1mut is therefore an emerging therapeutic approach, and inhibitors such as AG-120 and AG-881 have shown promising results in phase 1 and 2 clinical studies. However, detection of response to these therapies prior to changes in tumor growth can be challenging. The goal of this study was to identify non-invasive clinically translatable metabolic imaging biomarkers of IDH1mut inhibition that can serve to assess response. Methods: IDH1mut inhibition was confirmed using an enzyme assay and 1 H-and 13 C-magnetic resonance spectroscopy (MRS) were used to investigate the metabolic effects of AG-120 and AG-881 on two genetically engineered IDH1mut-expressing cell lines, NHAIDH1mut and U87IDH1mut. Results: 1 H-MRS indicated a significant decrease in steady-state 2-HG following treatment, as expected. This was accompanied by a significant 1 H-MRS-detectable increase in glutamate. However, other metabolites previously linked to 2-HG were not altered. 13 C-MRS also showed that the steady-state changes in glutamate were associated with a modulation in the flux of glutamine to both glutamate and 2-HG. Finally, hyperpolarized 13 C-MRS was used to show that the flux of -KG to both glutamate and 2-HG was modulated by treatment.","journal":"Theranostics","year":2020,"id":97914,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":473879,"name":"Chloé Najac","orcid":"0000-0002-7804-2281","position":1,"is_corresponding":false},{"id":483584,"name":"Pavithra Viswanath","orcid":"0000-0003-2980-3109","position":2,"is_corresponding":false},{"id":483585,"name":"Aliya Lakhani","orcid":"0000-0002-1275-9212","position":3,"is_corresponding":false},{"id":483586,"name":"Elavarasan Subramani","orcid":"0000-0003-2610-744X","position":4,"is_corresponding":false},{"id":483587,"name":"Georgios Batsios","orcid":"0000-0002-2340-1486","position":5,"is_corresponding":false},{"id":483588,"name":"Marina Radoul","orcid":"0000-0002-7843-2343","position":6,"is_corresponding":false},{"id":484157,"name":"Anne Marie Gillespie","orcid":null,"position":7,"is_corresponding":false},{"id":474447,"name":"Russell O. Pieper","orcid":null,"position":8,"is_corresponding":false},{"id":474448,"name":"Sabrina M. Ronen","orcid":null,"position":9,"is_corresponding":false},{"id":484156,"name":"Abigail R. Molloy","orcid":null,"position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-18T22:36:02.818637Z","pmid":"32754276","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}