Hyperpolarized [1-13C]Pyruvate Magnetic Resonance Spectroscopic Imaging for Evaluation of Early Response to Tyrosine Kinase Inhibition Therapy in Gastric Cancer.
Purpose: To evaluate the use of hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging (HP-13C MRSI) for quantitative measurement of early changes in glycolytic metabolism and its ability to predict response to pan-tyrosine kinase inhibitor (Pan-TKI) therapy in gastric cancer (GCa)....
| Publicado en: | Molecular Imaging & Biology Vol. 24; no. 5; pp. 769 - 780 |
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| Autores principales: | , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Springer Nature
Oct2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=159759414&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 159759414 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 15361632 KJU jtl: Molecular Imaging & Biology issn: 15361632 maglogo: N pubinfo: dt: Oct2022 vid: 24 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 159759414 159759414 NLM35467249 159759414 10.1007/s11307-022-01727-z NLM35467249 159759414 ppf: 769 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Hyperpolarized [1-13C]Pyruvate Magnetic Resonance Spectroscopic Imaging for Evaluation of Early Response to Tyrosine Kinase Inhibition Therapy in Gastric Cancer. aug: au: Esfahani, Shadi A. Callahan, Cody Rotile, Nicholas J. Heidari, Pedram Mahmood, Umar Caravan, Peter D. Grant, Aaron K. Yen, Yi-Fen affil: Divisionof Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA sug: subj: Fludeoxyglucose F 18 Stomach Neoplasms Drug Therapy Stomach Neoplasms Protein Kinase Inhibitors Pharmacodynamics Mice Oxidoreductases Metabolism Lactates Magnetic Resonance Spectroscopy Methods Transferases Metabolism Magnetic Resonance Imaging Methods Carrier Proteins Protein Kinase Inhibitors Therapeutic Use Animals Protein-Tyrosine Kinases Metabolism Carboxylic Acids Metabolism ab: Purpose: To evaluate the use of hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging (HP-13C MRSI) for quantitative measurement of early changes in glycolytic metabolism and its ability to predict response to pan-tyrosine kinase inhibitor (Pan-TKI) therapy in gastric cancer (GCa).Procedures: Pan-TKI afatinib-sensitive NCI-N87 and resistant SNU16 human GCa cells were assessed for GLUT1, hexokinase-II (HKII), lactate dehydrogenase (LDHA), phosphorylated AKT (pAKT), and phosphorylated MAPK (pMAPK) at 0-72 h of treatment with 0.1 μM afatinib. Subcutaneous NCI-N87 tumor-bearing nude mice underwent [18F]FDG PET/MRI and HP-13C MRSI at baseline and 4 days after treatment with afatinib 10 mg/kg/day or vehicle (n = 10/group). Changes in PET and HP-13C MRSI metabolic parameters were compared between the two groups. Imaging findings were correlated with tumor growth and histopathology over 3 weeks of treatment.Results: In vitro analysis showed a continuous decrease in LDHA, pAKT, and pMAPK in NCI-N87 compared to SNU16 cells within 72 h of treatment with afatinib, without a significant change in GLUT1 and HKII in either cell type. [18F]FDG PET of NCI-N87 tumors showed no significant change in PET measures at baseline and day 4 of treatment in either treatment group (SUVmean day 4/day 0: 2.7 ± 0.42/2.34 ± 0.38, p = 0.57 in the treated group vs. 1.73 ± 0.66/2.24 ± 0.43, p = 0.4 in the control group). HP-13C MRSI demonstrated significantly decreased lactate-to-pyruvate ratio (L/P) in treated tumors (L/P day 4/day 0: 0.83 ± 0.30/1.10 ± 0.20, p = 0.012 vs. 0.94 ± 0.20/0.98 ± 0.30, p = 0.75, in the treated vs. control group, respectively). Response to afatinib was confirmed with decreased tumor size over 3 weeks (11.10 ± 16.50 vs. 293.00 ± 79.30 mm3, p < 0.001, treated group vs. control group, respectively) and histopathologic evaluation.Conclusions: HP-13C MRSI is a more representative biomarker of early metabolic changes in response to pan-TKI in GCa than [18F]FDG PET and could be used for early prediction of response to targeted therapies. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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