Integrated Approach to Match Cancer Drug with Molecular Imaging Probe to Quantify Targeting and Predict Response.

Abstract

HomeRadiology: Imaging CancerVol. 2, No. 6 PreviousNext Research HighlightsFree AccessIntegrated Approach to Match Cancer Drug with Molecular Imaging Probe to Quantify Targeting and Predict ResponseGary D. LukerGary D. LukerGary D. LukerPublished Online:Nov 27 2020https://doi.org/10.1148/rycan.2020209035MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked InEmail Take-Away Points■ Major Focus: Identifying targeted cancer drugs and matching imaging agents through data from functional genetic screens.■ Key Result: Functional genetic screens showed that hepatocellular carcinoma is vulnerable to inhibition of lactate dehydrogenase, an enzyme that can be imaged by MR spectroscopy of hyperpolarized [1-13C]-pyruvate.■ Impact: The study opens a paradigm to integrate selection of a drug target and corresponding molecular imaging probe to quantify drug targeting and predict response to therapy.Drug development in oncology now focuses on targeting specific mutations and signaling pathways in cancer and stromal cells. Such drugs still fail in large numbers of patients due in part to a lack of imaging methods to accurately detect successful inhibition of a drug target. To overcome this limitation, Perkons et al analyzed publicly available data from screens of cancer cells for targetable vulnerabilities defined by CRISPR gene editing technology, a transformative technique recognized with the 2020 Nobel Prize in Chemistry. The investigators matched potential drug targets with enzymes and pathways that could be imaged with available imaging probes for hyperpolarized MR spectroscopy. Through this process, the team identified lactate dehydrogenase, an enzyme in glycolytic metabolism, as a therapeutic vulnerability in hepatocellular carcinoma and determined that hyperpolarized [1-13C]-pyruvate could be used to image inhibition of this enzyme.Using a rat model of hepatocellular carcinoma in a background of cirrhosis, dose-dependent inhibition of lactate dehydrogenase with a small molecule compound could be quantified by MR spectroscopy with hyperpolarized [1-13C]-pyruvate. The extent of inhibition correlated with effects of treatment to inhibit doubling of tumor volume measured by MRI. Increased levels of alanine, a metabolic byproduct of pyruvate, predicted successful response to therapy. These results establish an integrated approach to match a drug with a specific molecular imaging probe, which promises to improve the ability to rapidly predict response to cancer therapy with targeted inhibitors.Highlighted ArticlePerkons NR, Johnson O, Pilla G, et al. Functional genetic screening enables theranostic molecular imaging in cancer. Clin Cancer Res 2020; 26(17):4581–4589. doi: 10.1158/1078-0432.CCR-20-0826Highlighted ArticlePerkons NR, Johnson O, Pilla G et al. Functional genetic screening enables theranostic molecular imaging in cancer. Clin Cancer Res 2020; 26(17):4581–4589. doi: 10.1158/1078-0432.CCR-20-0826 Crossref, Medline, Google ScholarArticle HistoryPublished online: Nov 27 2020 FiguresReferencesRelatedDetailsRecommended Articles Monitoring Liver Tumor Ablation with MR Spectroscopy of Extracellular pHRadiology: Imaging Cancer2020Volume: 2Issue: 2Hyperpolarized 13C MRI: State of the Art and Future DirectionsRadiology2019Volume: 291Issue: 2pp. 273-284Precision Medicine and Radiogenomics in Breast Cancer: New Approaches toward Diagnosis and TreatmentRadiology2018Volume: 287Issue: 3pp. 732-747Immunotherapy and the Interventional Oncologist: Challenges and Opportunities—A Society of Interventional Oncology White PaperRadiology2019Volume: 292Issue: 1pp. 25-34Proliferative versus Nonproliferative Hepatocellular Carcinoma: Clinical and Imaging ImplicationsRadiology2021Volume: 300Issue: 3pp. 583-585See More RSNA Education Exhibits Assessing Immunotherapy with Functional and Molecular Imaging and Radiomics: Whence and WitherDigital Posters2019Precision Imaging Biomarkers for Enhanced Detection and Characterization of Primary and Metastatic Hepatic TumorsDigital Posters2017Imaging Biomarkers in Targeted Therapies: From Quantitative Imaging to RadiomicsDigital Posters2019 RSNA Case Collection Gallbladder CarcinomaRSNA Case Collection2021LI-RADS 4 RSNA Case Collection2021Primary HemochromatosisRSNA Case Collection2021 Vol. 2, No. 6 Metrics Downloaded 26 times Altmetric Score