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Effects of a Ketogenic Diet on [18F]FDG-PET Imaging in a Mouse Model of Lung Cancer

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Abstract

Purpose

Myocardial uptake can hamper visualization of lung tumors, atherosclerotic plaques, and inflammatory diseases in 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) studies because it leads to spillover in adjacent structures. Several preparatory pre-imaging protocols (including dietary restrictions and drugs) have been proposed to decrease physiological [18F]FDG uptake by the heart, although their effect on tumor glucose metabolism remains largely unknown. The objective of this study was to assess the effects of a ketogenic diet (as an alternative protocol to fasting) on tumor glucose metabolism assessed by [18F]FDG positron emission tomography (PET) in a mouse model of lung cancer.

Procedures

PET scans were performed 60 min after injection of 18.5 MBq of [18F]FDG. PET data were collected for 45 min, and an x-ray computed tomograph (CT) image was acquired after the PET scan. A PET/CT study was obtained for each mouse after fasting and after the ketogenic diet. Quantitative data were obtained from regions of interest in the left ventricular myocardium and lung tumor.

Results

Three days on a ketogenic diet decreased mean standard uptake value (SUVmean) in the myocardium (SUVmean 0.95 ± 0.36) more than one night of fasting (SUVmean 1.64 ± 0.93). Tumor uptake did not change under either dietary condition.

Conclusions

These results show that 3 days on high-fat diets prior to [18F]FDG-PET imaging does not change tumor glucose metabolism compared with one night of fasting, although high-fat diets suppress myocardial [18F]FDG uptake better than fasting.

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References

  1. Bertagna F, Biasiotto G, Giubbini R (2013) The role of F-18-fluorothymidine PET in oncology. Clin Transl Imaging 1:77–97

    Article  Google Scholar 

  2. Hoh CK (2007) Clinical use of FDG PET. Nucl Med Biol 34:737–742

    Article  CAS  PubMed  Google Scholar 

  3. Sathekge M, Maes A, Van de Wiele C (2013) FDG-PET imaging in HIV infection and tuberculosis. Semin Nucl Med 43:349–366

    Article  PubMed  Google Scholar 

  4. Fallahi B, Moasses-Ghafari B, Fard-Esfahani A et al (2017) Factors influencing the pattern and intensity of myocardial 18F-FDG uptake in oncologic PET-CT imaging. Iranian J Nucl Med 25:52–61

    CAS  Google Scholar 

  5. Maurer AH, Burshteyn M, Adler LP, Steiner RM (2011) How to differentiate benign versus malignant cardiac and paracardiac 18F FDG uptake at oncologic PET/CT. Radiographics 31:1287–1305

    Article  PubMed  Google Scholar 

  6. Lum DP, Wandell S, Ko J, Coel MN (2002) Reduction of myocardial 2-deoxy-2-[18F]fluoro-D-glucose uptake artifacts in positron emission tomography using dietary carbohydrate restriction. Mol Imaging Biol 4:232–237

    Article  PubMed  Google Scholar 

  7. Shreve PD, Anzai Y, Wahl RL (1999) Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. Radiographics 19:61–77 quiz 150-151

    Article  CAS  PubMed  Google Scholar 

  8. Gaeta C, Fernandez Y, Pavia J et al (2011) Reduced myocardial 18F-FDG uptake after calcium channel blocker administration. Initial observation for a potential new method to improve plaque detection. Eur J Nucl Med Mol Imaging 38:2018–2024

    Article  CAS  PubMed  Google Scholar 

  9. Tupper T, Wang Y, McDonagh E, et al. (2011) Utilizing Ketogenic Diet as an Alternative to Fasting in Preclinical 18F-FDG PET. In World Mol Imaging Congress (WMIC): 2011 Program Book

  10. Williams G, Kolodny GM (2008) Suppression of myocardial 18F-FDG uptake by preparing patients with a high-fat, low-carbohydrate diet. AJR Am J Roentgenol 190:W151–W156

    Article  PubMed  Google Scholar 

  11. Cussó L, Vaquero JJ, Bacharach S, Desco M (2014) Comparison of methods to reduce myocardial 18F-FDG uptake in mice: Calcium Channel blockers versus high-fat diets. PLoS One 9:e107999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cheng VY, Slomka PJ, Ahlen M, Thomson LEJ, Waxman AD, Berman DS (2010) Impact of carbohydrate restriction with and without fatty acid loading on myocardial 18F-FDG uptake during PET: a randomized controlled trial. J Nucl Cardiol 17:286–291

    Article  PubMed  Google Scholar 

  13. Kobayashi Y, Kumita S-i, Fukushima Y et al (2013) Significant suppression of myocardial 18F-fluorodeoxyglucose uptake using 24-h carbohydrate restriction and a low-carbohydrate, high-fat diet. J Cardiol 62:314–319

    Article  PubMed  Google Scholar 

  14. Nebeling LC, Miraldi F, Shurin SB, Lerner E (1995) Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr 14:202–208

    Article  CAS  Google Scholar 

  15. Skinner R, Trujillo A, Ma XJ, Beierle EA (2009) Ketone bodies inhibit the viability of human neuroblastoma cells. J Pediatr Surg 44:212–216

    Article  PubMed  Google Scholar 

  16. Seyfried TN, Sanderson TM, El-Abbadi MM et al (2003) Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer 89:1375–1382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Abdelwahab MG, Fenton KE, Preul MC, Rho JM, Lynch A, Stafford P, Scheck AC (2012) The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS One 7:e36197

    Article  PubMed  PubMed Central  Google Scholar 

  18. Caso J, Masko EM, Thomas JA et al (2013) The effect of carbohydrate restriction on prostate cancer tumor growth in a castrate mouse xenograft model. Prostate 73:449–454

    Article  CAS  PubMed  Google Scholar 

  19. Poff AM, Ari C, Seyfried TN, D’Agostino DP (2013) The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer. PLoS One 8:e65522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ambrogio C, Cámara JA, Nieto P et al (2015) Analysis of murine lung tumors by micro PET-CT imaging. In Bio-protocol:e1692

  21. Wykrzykowska J, Lehman S, Williams G, Parker JA, Palmer MR, Varkey S, Kolodny G, Laham R (2009) Imaging of inflamed and vulnerable plaque in coronary arteries with 18F-FDG PET/CT in patients with suppression of myocardial uptake using a low-carbohydrate, high-fat preparation. J Nucl Med 50:563–568

    Article  PubMed  Google Scholar 

  22. Bertagna F, Bisleri G, Motta F, Merli G, Cossalter E, Lucchini S, Biasiotto G, Bosio G, Terzi A, Muneretto C, Giubbini R (2012) Possible role of F18-FDG-PET/CT in the diagnosis of endocarditis: preliminary evidence from a review of the literature. Int J Cardiovasc Imaging 28:1417–1425

    Article  PubMed  Google Scholar 

  23. Abella M, Vaquero JJ, Sisniega A, Pascau J, Udías A, García V, Vidal I, Desco M (2012) Software architecture for multi-bed FDK-based reconstruction in X-ray CT scanners. Comput Meth Prog Bio 107:218–232

    Article  CAS  Google Scholar 

  24. Wang Y, Seidel J, Tsui BMW, Vaquero JJ, Pomper MG (2006) Performance evaluation of the GE Healthcare eXplore VISTA dual-ring small-animal PET scanner. J Nucl Med 47:1891–1900

    PubMed  Google Scholar 

  25. Woo S-K, Lee TS, Kim KM, Kim JY, Jung JH, Kang JH, Cheon GJ, Choi CW, Lim SM (2008) Anesthesia condition for 18F-FDG imaging of lung metastasis tumors using small animal PET. Nucl Med Biol 35:143–150

    Article  CAS  PubMed  Google Scholar 

  26. Huebbers CU, Adam AC, Preuss SF, Schiffer T, Schilder S, Guntinas-Lichius O, Schmidt M, Klussmann JP, Wiesner RJ (2015) High glucose uptake unexpectedly is accompanied by high levels of the mitochondrial β-F1-ATPase subunit in head and neck squamous cell carcinoma. Oncotarget 6:36172–36184

    Article  PubMed  PubMed Central  Google Scholar 

  27. Guckenberger M, Rudofsky L, Andratschke N (2015) FDG-PET imaging for advanced radiotherapy treatment of non-small-cell lung Cancer. In: Hodler J, von Schulthess GK, Kubik-Huch RA, Zollikofer CL (eds) Diseases of the chest and heart 2015–2018. Springer Milan, pp 177–182

  28. García-Beccaria M, Martínez P, Méndez-Pertuz M et al (2015) Therapeutic inhibition of TRF1 impairs the growth of p53-deficient K-Ras(G12V)-induced lung cancer by induction of telomeric DNA damage. EMBO Mol Med 7:930–949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lindholm P, Minn H, Leskinen-Kallio S, Bergman J, Ruotsalainen U, Joensuu H (1993) Influence of the blood glucose concentration on FDG uptake in Cancer—a PET study. J Nucl Med 34:1–6

    CAS  PubMed  Google Scholar 

  30. Rubello D, Gordien P, Morliere C et al (2015) Variability of hepatic 18F-FDG uptake at interim PET in patients with Hodgkin lymphoma. Clin Nucl Med 40:e405–e410

    Article  PubMed  Google Scholar 

  31. Wahl RL, Henry CA, Ethier SP (1992) Serum glucose: effects on tumor and normal tissue accumulation of 2-[F-18]-fluoro-2-deoxy-D-glucose in rodents with mammary carcinoma. Radiology 183:643–647

    Article  CAS  PubMed  Google Scholar 

  32. Hindryckx P, Staelens S, Devisscher L, Deleye S, de Vos F, Delrue L, Peeters H, Laukens D, de Vos M (2011) Longitudinal quantification of inflammation in the murine dextran sodium sulfate-induced colitis model using muPET/CT. Inflamm Bowel Dis 17:2058–2064

    Article  CAS  PubMed  Google Scholar 

  33. Kestler M, Muñoz P, Rodríguez-Créixems M et al (2014) Role of 18F-FDG PET in patients with infectious endocarditis. J Nucl Med 55:1093–1098

    Article  CAS  PubMed  Google Scholar 

  34. Ravasi L, Shimoji K, Soto-Montenegro ML, Esaki T, Seidel J, Sokoloff L, Schmidt K (2011) Use of [18F]fluorodeoxyglucose and the ATLAS small animal PET scanner to examine cerebral functional activation by whisker stimulation in unanesthetized rats. Nucl Med Commun 32:336–342

    Article  PubMed  PubMed Central  Google Scholar 

  35. Thanos PK, Michaelides M, Gispert JD, Pascau J, Soto-Montenegro ML, Desco M, Wang R, Wang GJ, Volkow ND (2008) Differences in response to food stimuli in a rat model of obesity: in-vivo assessment of brain glucose metabolism. Int J Obes 32:1171–1179

    Article  CAS  Google Scholar 

  36. Stanley WC, Recchia FA, Lopaschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85:1093–1129

    Article  CAS  PubMed  Google Scholar 

  37. Harisankar C, Mittal B, Agrawal K, Abrar M et al (2011) Utility of high fat and low carbohydrate diet in suppressing myocardial FDG uptake. J Nucl Cardiol 18:926–936

    Article  PubMed  Google Scholar 

  38. López-Ríos F, Sánchez-Aragó M, García-García E, Ortega ÁD, Berrendero JR, Pozo-Rodríguez F, López-Encuentra Á, Ballestín C, Cuezva JM (2007) Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of carcinomas. Cancer Res 67:9013–9017

    Article  PubMed  Google Scholar 

  39. Cuezva JM, Chen G, Alonso AM, Isidoro A, Misek DE, Hanash SM, Beer DG (2004) The bioenergetic signature of lung adenocarcinomas is a molecular marker of cancer diagnosis and prognosis. Carcinogenesis 25:1157–1163

    Article  CAS  PubMed  Google Scholar 

  40. Sánchez-Aragó M, Formentini L, Cuezva JM (2013) Mitochondria-mediated energy adaption in Cancer: the H(+)-ATP synthase-geared switch of metabolism in human tumors. Antioxid Redox Signal 19:285–298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270

    CAS  Google Scholar 

  42. Langen KJ, Braun U, Rota Kops E, Herzog H, Kuwert T, Nebeling B, Feinendegen LE (1993) The influence of plasma glucose levels on fluorine-18-fluorodeoxyglucose uptake in bronchial carcinomas. J Nucl Med 34:355–359

    CAS  PubMed  Google Scholar 

  43. Wong KP, Sha W, Zhang X, Huang SC (2011) Effects of administration route, dietary condition, and blood glucose level on kinetics and uptake of 18F-FDG in mice. J Nucl Med 52:800–807

    Article  PubMed  PubMed Central  Google Scholar 

  44. Stanley WC (2001) Changes in cardiac metabolism: a critical step from stable angina to ischaemic cardiomyopathy. Eur Heart J Suppl 3:O2–O7

    Article  Google Scholar 

  45. Fueger BJ, Czernin J, Hildebrandt I, Tran C, Halpern BS, Stout D, Phelps ME, Weber WA (2006) Impact of animal handling on the results of 18FDG PET studies in mice. J Nucl Med 47:999–1006

    CAS  PubMed  Google Scholar 

  46. Toyama H, Ichise M, Liow JS, Vines DC, Seneca NM, Modell KJ, Seidel J, Green MV, Innis RB (2004) Evaluation of anesthesia effects on [18F]FDG uptake in mouse brain and heart using small animal PET. Nucl Med Biol 31:251–256

    Article  CAS  PubMed  Google Scholar 

  47. Jensen T, Kiersgaard M, Sørensen D, Mikkelsen LF (2013) Fasting of mice: a review. Lab Anim 47:225–240

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank Alexandra de Francisco and Yolanda Sierra for their excellent work with animal preparation and imaging protocols.

Funding

This work was partially supported by Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and cofinanciado con Fondos Estructurales de la Unión Europea. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).

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Authors and Affiliations

  1. Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Avenida de la Universidad 30, 28911, Leganés, Madrid, Spain

    Lorena Cussó & Manuel Desco

  2. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain

    Lorena Cussó & Manuel Desco

  3. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain

    Lorena Cussó & Manuel Desco

  4. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain

    Lorena Cussó & Manuel Desco

  5. Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain

    Mónica Musteanu, Francisca Mulero & Mariano Barbacid

Authors
  1. Lorena Cussó
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  2. Mónica Musteanu
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  3. Francisca Mulero
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  4. Mariano Barbacid
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  5. Manuel Desco
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Corresponding author

Correspondence to Lorena Cussó.

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Ethics Statement

All animal procedures were approved by the Animal Experimentation Ethics Committee of Hospital General Universitario Gregorio Marañón (ES280790000087) and the Ethics Committees of CNIO and the Carlos III Health Institute, Madrid, and performed according to European regulations (2010/63/UE) and National regulations (RD 53/2013).

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The authors declare that they have no conflicts of interest.

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Cussó, L., Musteanu, M., Mulero, F. et al. Effects of a Ketogenic Diet on [18F]FDG-PET Imaging in a Mouse Model of Lung Cancer. Mol Imaging Biol 21, 279–285 (2019). https://doi.org/10.1007/s11307-018-1233-8

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