Imaging tumor metabolism using positron emission tomography.

Positron emission tomography (PET) is an extraordinarily sensitive clinical imaging modality for interrogating tumor metabolism. Radiolabeled PET substrates can be traced at subphysiological concentrations, allowing noninvasive imaging of metabolism and intratumoral heterogeneity in systems ranging from advanced cancer models to patients in the clinic. There are a wide range of novel and more established PET radiotracers, which can be used to investigate various aspects of the tumor, including carbohydrate, amino acid, and fatty acid metabolism. In this review, we briefly discuss the more established metabolic tracers and describe recent work on the development of new tracers. Some of the unanswered questions in tumor metabolism are considered alongside new technical developments, such as combined PET/magnetic resonance imaging scanners, which could provide new imaging solutions to some of the outstanding diagnostic challenges facing modern cancer medicine.

[1]  C. Brennan,et al.  Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo , 2015, Science Translational Medicine.

[2]  M. Spector,et al.  Organoid Models of Human and Mouse Ductal Pancreatic Cancer , 2015, Cell.

[3]  N. Sunaga,et al.  Clinicopathological significance of ASC amino acid transporter‐2 expression in pancreatic ductal carcinoma , 2015, Histopathology.

[4]  Joshua D. Rabinowitz,et al.  The return of metabolism: biochemistry and physiology of the pentose phosphate pathway , 2014, Biological reviews of the Cambridge Philosophical Society.

[5]  M. Goodman,et al.  System a amino acid transport-targeted brain and systemic tumor PET imaging agents 2-amino-3-[(18)F]fluoro-2-methylpropanoic acid and 3-[(18)F]fluoro-2-methyl-2-(methylamino)propanoic acid. , 2015, Nuclear medicine and biology.

[6]  Acetate Fuels the Cancer Engine , 2015, Cell.

[7]  R. Deberardinis,et al.  Acetate Is a Bioenergetic Substrate for Human Glioblastoma and Brain Metastases , 2014, Cell.

[8]  M. Merritt,et al.  Hyperpolarized Magnetic Resonance as a Sensitive Detector of Metabolic Function , 2014, Biochemistry.

[9]  T. Arumugam,et al.  Preliminary evaluation of 1'-[(18)F]fluoroethyl-β-D-lactose ([(18)F]FEL) for detection of pancreatic cancer in nude mouse orthotopic xenografts. , 2014, Nuclear medicine and biology.

[10]  A. Buck,et al.  Comparison of the Amino Acid Tracers 18F-FET and 18F-DOPA in High-Grade Glioma Patients , 2014, The Journal of Nuclear Medicine.

[11]  J. Swinnen,et al.  Cancer Cells Differentially Activate and Thrive on De Novo Lipid Synthesis Pathways in a Low-Lipid Environment , 2014, PloS one.

[12]  E. Gottlieb,et al.  Preclinical Evaluation of 3-18F-Fluoro-2,2-Dimethylpropionic Acid as an Imaging Agent for Tumor Detection , 2014, The Journal of Nuclear Medicine.

[13]  H. Kung,et al.  [18F](2S,4S)-4-(3-Fluoropropyl)glutamine as a Tumor Imaging Agent , 2014, Molecular pharmaceutics.

[14]  D. Neal,et al.  Late Imaging with [1-11C]Acetate Improves Detection of Tumor Fatty Acid Synthesis with PET , 2014, The Journal of Nuclear Medicine.

[15]  M. Phelps,et al.  Positron emission tomography probe demonstrates a striking concentration of ribose salvage in the liver , 2014, Proceedings of the National Academy of Sciences.

[16]  V. Ambrosini,et al.  18F-FACBC compared with 11C-choline PET/CT in patients with biochemical relapse after radical prostatectomy: a prospective study in 28 patients. , 2014, Clinical genitourinary cancer.

[17]  Christine A. Morton,et al.  Functional Imaging of Oxidative Stress with a Novel PET Imaging Agent, 18F-5-Fluoro-l-Aminosuberic Acid , 2014, The Journal of Nuclear Medicine.

[18]  Y. Tomizawa,et al.  ASC amino-acid transporter 2 (ASCT2) as a novel prognostic marker in non-small cell lung cancer , 2014, British Journal of Cancer.

[19]  P. Choyke,et al.  Localized prostate cancer detection with 18F FACBC PET/CT: comparison with MR imaging and histopathologic analysis. , 2014, Radiology.

[20]  R. Deberardinis,et al.  A novel radiotracer to image glycogen metabolism in tumors by positron emission tomography. , 2014, Cancer research.

[21]  K. Brindle,et al.  Versatile and enhanced tumour modelling in mice via somatic cell transduction , 2014, The Journal of pathology.

[22]  Rohini Sharma,et al.  Biodistribution and Radiation Dosimetry of Deuterium-Substituted 18F-Fluoromethyl-[1, 2-2H4]Choline in Healthy Volunteers , 2014, The Journal of Nuclear Medicine.

[23]  C. Cordon-Cardo,et al.  RapidCaP, a novel GEM model for metastatic prostate cancer analysis and therapy, reveals myc as a driver of Pten-mutant metastasis. , 2014, Cancer discovery.

[24]  I. Huijbers,et al.  Rapid target gene validation in complex cancer mouse models using re-derived embryonic stem cells , 2014, EMBO molecular medicine.

[25]  Mikko I. Kettunen,et al.  Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose , 2013, Nature Medicine.

[26]  T. Bjørge,et al.  Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer—A large nested case–control study within the JANUS cohort in Norway , 2014, International journal of cancer.

[27]  N. Tamaki,et al.  Improved spillover correction model to quantify myocardial blood flow by 11C-acetate PET: comparison with 15O-H2O PET , 2014, Annals of Nuclear Medicine.

[28]  S. Ametamey,et al.  Imaging Tumour ATB0,+ Transport Activity by PET with the Cationic Amino Acid O-2((2-[18F]fluoroethyl)methyl-amino)ethyltyrosine , 2014, Molecular Imaging and Biology.

[29]  Tomoya Mizuno,et al.  Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma , 2013, BMC Cancer.

[30]  Z N Oltvai,et al.  Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells , 2013, Cell Death and Disease.

[31]  E. Aboagye,et al.  Synthesis of [18F]fluoro-pivalic acid: An improved PET imaging probe for the fatty acid synthesis pathway in tumours , 2013 .

[32]  P. Larson,et al.  Metabolic Imaging of Patients with Prostate Cancer Using Hyperpolarized [1-13C]Pyruvate , 2013, Science Translational Medicine.

[33]  H. Fukuda,et al.  In Vitro and In Vivo Characterization of 2-Deoxy-2-18F-Fluoro-d-Mannose as a Tumor-Imaging Agent for PET , 2013, The Journal of Nuclear Medicine.

[34]  J. Locasale.  Serine, glycine and one-carbon units: cancer metabolism in full circle , 2013, Nature Reviews Cancer.

[35]  L. Bachmann,et al.  The role of 11C-choline and 18F-fluorocholine positron emission tomography (PET) and PET/CT in prostate cancer: a systematic review and meta-analysis. , 2013, European urology.

[36]  J. McConathy,et al.  Radiolabeled Amino Acids for Oncologic Imaging , 2013, The Journal of Nuclear Medicine.

[37]  B. Van Houten,et al.  Metabolic symbiosis in cancer: Refocusing the Warburg lens , 2013, Molecular carcinogenesis.

[38]  Pier Paolo Pandolfi,et al.  Cancer metabolism: fatty acid oxidation in the limelight , 2013, Nature Reviews Cancer.

[39]  L. Carroll,et al.  Design and synthesis of novel 18F-radiolabelled glucosamine derivatives for cancer imaging , 2013 .

[40]  Luc Tremblay,et al.  Conversion of arterial input functions for dual pharmacokinetic modeling using Gd‐DTPA/MRI and 18F‐FDG/PET , 2013, Magnetic resonance in medicine.

[41]  G. Tomasi,et al.  Introduction to the analysis of PET data in oncology , 2013, Journal of Pharmacokinetics and Pharmacodynamics.

[42]  P. Kalivas,et al.  The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities. , 2013, Antioxidants & redox signaling.

[43]  Jae Seung Kim,et al.  (4S)-4-(3-18F-Fluoropropyl)-l-Glutamate for Imaging of xC¯ Transporter Activity in Hepatocellular Carcinoma Using PET: Preclinical and Exploratory Clinical Studies , 2013, The Journal of Nuclear Medicine.

[44]  H. Kung,et al.  Comparative Evaluation of 18F-Labeled Glutamic Acid and Glutamine as Tumor Metabolic Imaging Agents , 2012, The Journal of Nuclear Medicine.

[45]  L. Carroll,et al.  Radiosynthesis and in vivo tumor uptake of 2-deoxy-2-[(18)F]fluoro-myo-inositol. , 2012, Bioorganic & medicinal chemistry letters.

[46]  H. Kung,et al.  Synthesis and evaluation of 18F labeled alanine derivatives as potential tumor imaging agents. , 2012, Nuclear medicine and biology.

[47]  D. Sabatini,et al.  Cancer cell metabolism: one hallmark, many faces. , 2012, Cancer discovery.

[48]  E. Mittra,et al.  Exploratory Clinical Trial of (4S)-4-(3-[18F]fluoropropyl)-l-glutamate for Imaging xC− Transporter Using Positron Emission Tomography in Patients with Non–Small Cell Lung or Breast Cancer , 2012, Clinical Cancer Research.

[49]  Keigo Endo,et al.  Transport of 3-Fluoro-l-α-Methyl-Tyrosine by Tumor-Upregulated L-Type Amino Acid Transporter 1: A Cause of the Tumor Uptake in PET , 2012, The Journal of Nuclear Medicine.

[50]  N. Sunaga,et al.  Prognostic significance of L-type amino-acid transporter 1 expression in surgically resected pancreatic cancer , 2012, British Journal of Cancer.

[51]  Aik Choon Tan,et al.  Patient-derived tumour xenografts as models for oncology drug development , 2012, Nature Reviews Clinical Oncology.

[52]  V. Mootha,et al.  Metabolite Profiling Identifies a Key Role for Glycine in Rapid Cancer Cell Proliferation , 2012, Science.

[53]  Wei Liu,et al.  The Proline Regulatory Axis and Cancer , 2012, Front. Oncol..

[54]  G Tomasi,et al.  Double-input compartmental modeling and spectral analysis for the quantification of positron emission tomography data in oncology , 2012, Physics in medicine and biology.

[55]  Dmitry Soloviev,et al.  [(18)F]FLT: an imaging biomarker of tumour proliferation for assessment of tumour response to treatment. , 2012, European journal of cancer.

[56]  John C Waterton,et al.  Qualification of imaging biomarkers for oncology drug development. , 2012, European journal of cancer.

[57]  John O. Prior,et al.  Performance of 18F-Fluoro-Ethyl-Tyrosine (18F-FET) PET for the Differential Diagnosis of Primary Brain Tumor: A Systematic Review and Metaanalysis , 2012, The Journal of Nuclear Medicine.

[58]  G. Tomasi,et al.  Evaluation of Deuterated 18F- and 11C-Labeled Choline Analogs for Cancer Detection by Positron Emission Tomography , 2012, Clinical Cancer Research.

[59]  L. Chodosh,et al.  Preparation and Characterization of l-[5-11C]-Glutamine for Metabolic Imaging of Tumors , 2012, The Journal of Nuclear Medicine.

[60]  Federico Turkheimer,et al.  Importance of Quantification for the Analysis of PET Data in Oncology: Review of Current Methods and Trends for the Future , 2012, Molecular Imaging and Biology.

[61]  L. Bidaut,et al.  Pharmacokinetics, Metabolism, Biodistribution, Radiation Dosimetry, and Toxicology of 18F-Fluoroacetate (18F-FACE) in Non-human Primates , 2012, Molecular Imaging and Biology.

[62]  Aditya Bansal,et al.  Fluorine-18 labeled thia fatty acids for PET imaging of fatty acid oxidation in heart and cancer , 2011 .

[63]  L. Chodosh,et al.  PET Imaging of Glutaminolysis in Tumors by 18F-(2S,4R)4-Fluoroglutamine , 2011, The Journal of Nuclear Medicine.

[64]  M. Schwaiger,et al.  How Many PET Tracers Do We Need? , 2011, The Journal of Nuclear Medicine.

[65]  S. Gambhir,et al.  GLUT 5 Is Not Over-Expressed in Breast Cancer Cells and Patient Breast Cancer Tissues , 2011, PLoS ONE.

[66]  M. V. Vander Heiden,et al.  Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. , 2011, Annual review of cell and developmental biology.

[67]  F. Gallagher,et al.  Hyperpolarized 13C MRI and PET: In Vivo Tumor Biochemistry , 2011, The Journal of Nuclear Medicine.

[68]  F. Gallagher,et al.  Tumor imaging using hyperpolarized 13C magnetic resonance spectroscopy , 2011, Magnetic resonance in medicine.

[69]  L. Dinkelborg,et al.  Specific PET Imaging of xC− Transporter Activity Using a 18F-Labeled Glutamate Derivative Reveals a Dominant Pathway in Tumor Metabolism , 2011, Clinical Cancer Research.

[70]  Ralph J DeBerardinis,et al.  Role of Glutamine in Cancer: Therapeutic and Imaging Implications , 2011, The Journal of Nuclear Medicine.

[71]  W. Pao,et al.  How genetically engineered mouse tumor models provide insights into human cancers. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[72]  S. Keiding,et al.  The potential use of 2-[18F]fluoro-2-deoxy-D-galactose as a PET/CT tracer for detection of hepatocellular carcinoma , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[73]  Gabriele Stoffels,et al.  Prognostic value of early [18F]fluoroethyltyrosine positron emission tomography after radiochemotherapy in glioblastoma multiforme. , 2011, International journal of radiation oncology, biology, physics.

[74]  M. Wuest,et al.  Radiopharmacological evaluation of 6-deoxy-6-[18F]fluoro-D-fructose as a radiotracer for PET imaging of GLUT5 in breast cancer. , 2011, Nuclear medicine and biology.

[75]  M. Ohmura,et al.  CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. , 2011, Cancer cell.

[76]  B. Wolffenbuttel,et al.  Tyrosine positron emission tomography and protein synthesis rate in pituitary adenoma: different effects of surgery and radiation therapy. , 2011, Radiotherapy and Oncology.

[77]  S. Ametamey,et al.  4-[18F]fluoroglutamic acid (BAY 85-8050), a new amino acid radiotracer for PET imaging of tumors: synthesis and in vitro characterization. , 2011, Journal of medicinal chemistry.

[78]  J. Gelovani,et al.  Radiosynthesis of N5-[18F]fluoroacetylornithine (N5-[18F]FAO) for PET imaging of ornithine decarboxylase (ODC) in malignant tumors , 2011 .

[79]  S. Luthra,et al.  Radiosynthesis and pre-clinical evaluation of [(18)F]fluoro-[1,2-(2)H(4)]choline. , 2011, Nuclear medicine and biology.

[80]  P. Iozzo,et al.  Fatty acid metabolism in the liver, measured by positron emission tomography, is increased in obese individuals. , 2010, Gastroenterology.

[81]  M. Pandey,et al.  Synthesis and Preliminary Evaluation of 18-18F-Fluoro-4-Thia-Oleate as a PET Probe of Fatty Acid Oxidation , 2010, The Journal of Nuclear Medicine.

[82]  Terry K. Smith,et al.  The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine , 2010, IUBMB life.

[83]  J. Viola,et al.  Lipid droplets in inflammation and cancer. , 2010, Prostaglandins, leukotrienes, and essential fatty acids.

[84]  K. Nakanishi,et al.  LAT1 expression in non-small-cell lung carcinomas: analyses by semiquantitative reverse transcription-PCR (237 cases) and immunohistochemistry (295 cases). , 2010, Lung cancer.

[85]  E. Malveaux,et al.  Synthesis, radiolabeling, and biological evaluation of (R)- and (S)-2-amino-3-[(18)F]fluoro-2-methylpropanoic acid (FAMP) and (R)- and (S)-3-[(18)F]fluoro-2-methyl-2-N-(methylamino)propanoic acid (NMeFAMP) as potential PET radioligands for imaging brain tumors. , 2010, Journal of medicinal chemistry.

[86]  G. Brooks,et al.  Cell–cell and intracellular lactate shuttles , 2009, The Journal of physiology.

[87]  Steven M Larson,et al.  2-18F-Fluoropropionic Acid as a PET Imaging Agent for Prostate Cancer , 2009, Journal of Nuclear Medicine.

[88]  Y. Fujibayashi,et al.  Tumor uptake of radiolabeled acetate reflects the expression of cytosolic acetyl-CoA synthetase: implications for the mechanism of acetate PET. , 2009, Nuclear medicine and biology.

[89]  Ferdia A Gallagher,et al.  A comparison between radiolabeled fluorodeoxyglucose uptake and hyperpolarized (13)C-labeled pyruvate utilization as methods for detecting tumor response to treatment. , 2009, Neoplasia.

[90]  Jens Sörensen,et al.  [18F]Fluoroacetate is not a functional analogue of [11C]acetate in normal physiology , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[91]  Anthony Mancuso,et al.  Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction , 2008, Proceedings of the National Academy of Sciences.

[92]  D. Valenti,et al.  Mitochondria and l‐lactate metabolism , 2008, FEBS letters.

[93]  P. Pedersen.  Voltage dependent anion channels (VDACs): a brief introduction with a focus on the outer mitochondrial compartment’s roles together with hexokinase-2 in the “Warburg effect” in cancer , 2008, Journal of Bioenergetics and Biomembranes.

[94]  F. Floeth,et al.  Prognostic Value of 18F-Fluoroethyl-l-Tyrosine PET and MRI in Small Nonspecific Incidental Brain Lesions , 2008, Journal of Nuclear Medicine.

[95]  Ciprian Catana,et al.  Simultaneous PET-MRI: a new approach for functional and morphological imaging , 2008, Nature Medicine.

[96]  Y. Kato,et al.  Cancer Detection Using a PET Tracer, 11C-Glycylsarcosine, Targeted to H+/Peptide Transporter , 2008, Journal of Nuclear Medicine.

[97]  R. Coleman,et al.  Recommendations on the Use of 18F-FDG PET in Oncology , 2008, Journal of Nuclear Medicine.

[98]  S. Kridel,et al.  1-11C-Acetate as a PET Radiopharmaceutical for Imaging Fatty Acid Synthase Expression in Prostate Cancer , 2008, Journal of Nuclear Medicine.

[99]  Ralph J Deberardinis,et al.  Brick by brick: metabolism and tumor cell growth. , 2008, Current opinion in genetics & development.

[100]  Kevin Brindle,et al.  New approaches for imaging tumour responses to treatment , 2008, Nature Reviews Cancer.

[101]  Johan Nuyts,et al.  1-11C-Acetate Kinetics of Prostate Cancer , 2008, Journal of Nuclear Medicine.

[102]  R. Deberardinis,et al.  Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis , 2007, Proceedings of the National Academy of Sciences.

[103]  P. Pedersen,et al.  Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers’ most common phenotypes, the “Warburg Effect”, i.e., elevated glycolysis in the presence of oxygen , 2007, Journal of bioenergetics and biomembranes.

[104]  David A. Tuveson,et al.  Maximizing mouse cancer models , 2007, Nature Reviews Cancer.

[105]  H. Nawashiro,et al.  L‐type amino acid transporter 1 as a potential molecular target in human astrocytic tumors , 2006, International journal of cancer.

[106]  B. Fuchs,et al.  Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? , 2005, Seminars in cancer biology.

[107]  B. Långström,et al.  Inhibition of carnitine-acyl transferase I by oxfenicine studied in vivo with [11C]-labeled fatty acids. , 2005, Nuclear medicine and biology.

[108]  R. Hruban,et al.  Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma , 2005, Modern Pathology.

[109]  K. Hamacher,et al.  O-(2-[18F]fluorethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[110]  L. Christa,et al.  HIP/PAP, a C-type lectin overexpressed in hepatocellular carcinoma, binds the RII alpha regulatory subunit of cAMP-dependent protein kinase and alters the cAMP-dependent protein kinase signalling. , 2004, European journal of biochemistry.

[111]  Kent Lai,et al.  Alternative pathways of galactose assimilation: could inverse metabolic engineering provide an alternative to galactosemic patients? , 2004, Metabolic engineering.

[112]  F. Soussaline,et al.  Brain tumor protein synthesis and histological grades: A study by positron emission tomography (PET) with C11-L-Methionine , 2004, Journal of Neuro-Oncology.

[113]  Thomas Czech,et al.  Brain tumour imaging with PET: a comparison between [18F]fluorodopa and [11C]methionine , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[114]  S. Gambhir.  Molecular imaging of cancer with positron emission tomography , 2002, Nature Reviews Cancer.

[115]  S. Gunn,et al.  Positron Emission Tomography Compartmental Models , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[116]  T. Smith,et al.  The rate-limiting step for tumor [18F]fluoro-2-deoxy-D-glucose (FDG) incorporation. , 2001, Nuclear medicine and biology.

[117]  R. Coleman,et al.  Synthesis and evaluation of 18F-labeled choline as an oncologic tracer for positron emission tomography: initial findings in prostate cancer. , 2001, Cancer research.

[118]  Wolfgang A. Weber,et al.  O-(2-[18F]Fluoroethyl)-l-tyrosine and l-[methyl-11C]methionine uptake in brain tumours: initial results of a comparative study , 2000, European Journal of Nuclear Medicine.

[119]  M. Bergström,et al.  Uptake of 14C- and 11C-labeled glutamate, glutamine and aspartate in vitro and in vivo. , 2000, Anticancer research.

[120]  Shelly C. Lu.  Regulation of hepatic glutathione synthesis: current concepts and controversies , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[121]  W. Molenaar,et al.  Protein synthesis rate measured with l-[1-11C]tyrosine positron emission tomography correlates with mitotic activity and MIB-1 antibody-detected proliferation in human soft tissue sarcomas , 1999, European Journal of Nuclear Medicine.

[122]  N. Alpert,et al.  Muscle protein synthesis by positron-emission tomography with L-[methyl-11C]methionine in adult humans. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[123]  J. van den Hoff,et al.  A kinetic model for cardiac PET with [1-carbon-11]-acetate. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[124]  A. Willemsen,et al.  Brain tumors: L-[1-C-11]tyrosine PET for visualization and quantification of protein synthesis rate. , 1995, Radiology.

[125]  U. Haberkorn,et al.  Carbon‐11 labelled analogs of alanine by the strecker synthesis , 1995 .

[126]  J C Mazziotta,et al.  Estimation of Local Cerebral Protein Synthesis Rates with L-[1-11C]Leucine and PET: Methods, Model, and Results in Animals and Humans , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[127]  R A Brooks,et al.  Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography , 1982, Neurology.

[128]  D. M. Greenberg,et al.  Tracer studies on the metabolism of the Gardner lymphosarcoma. III. The rate of radioactive alanine and glycine uptake into the protein of lymphosarcoma cells and normal spleen cells. , 1951, Cancer research.