Correlation of cancer status and brown adipose tissue activity on 18F-flourodeoxyglucose positron emission tomography/computed tomography

Year 2022, , 52 - 58, 26.03.2022

Mine Araz , Başak Gülpınar , Pınar Gündüz , Elgin Özkan , Mustafa Şahin

https://doi.org/10.18663/tjcl.1026201

Abstract

Aim: In this study, we aimed to compare brown adipose tissue (BAT) activity on 18F-Flourodeoxyglucose Positron Emission Tomography (PET)/Computed Tomography(CT) in patients with and without active cancer.
Material and Methods: Results of the patients who underwent 18F-FDG PET/CT between January 2014 and February 2018 in Nuclear Medicine Department were evaluated retrospectively. Age, gender, body mass index (BMI), serum levels of glucose, bilirubin, total cholesterol (T-chol), low-density lipoprotein (LDL) and triglyceride (TG) of the patients were noted from the hospital database. Mean outdoor temperature of the day during PET/CT imaging was searched from National Weather Service archives. Diagnosis and disease activity status on PET/CT imaging were evaluated retrospectively. Standardized uptake value (SUV) and brown adipose tissue volume (BAV) were calculated on PET/CT images. Additionally, hepatic attenuation index and subcutaneous adipose tissue thickness (SCATT) were calculated from CT images. Difference between median SUV and BAV among groups with and without active cancer was analyzed.
Results: Totally 78 (54 F; 24 M; mean age 34.415.6) patients who underwent 18F-FDG PET/CT for different oncological indications were included in the analysis. All the patients had different degrees of BAT uptake on PET/CT images. Median (min-max) values for SUV, BAV and SCATT were found as 8.0 (2.7-37.0), 26.9 (2.1- 116.0) cm3 and 15.0 (3.0- 46.0) mm, respectively. Hepatic attenuation index was 0-5%, 6-30% and >30% in 56 (71%), 20 (26%) and 2 (3%) patients, respectively. Active disease was observed in 26 (33%) patients during PET/CT imaging. In the evaluation of the distribution of the adipose tissue parameters, median SUV (p=0.008) and BAV (p=0.008) of groups with and without active cancer were found statistically significant.
Conclusion: BAT activity in patients with active cancer seems to be higher than that in patients without active disease, supporting the possible role of adipose tissue activation on cancer development and progression.

Keywords

Brown adipose tissue, positron emission tomography, Fluorodeoxyglucose F18

18F-Fluorodeoksiglukoz positron emisyon tomografi/bilgisayarlı tomografi’de kahverengi yağ dokusu aktivitesi ve kanser durumunun korelasyonu

Abstract

Amaç: Bu çalışmada 18F-Fluorodeksiglukoz (FDG) positron emisyon tomografi/ bilgisayarlı tomografi (BT)’de aktif kanseri olan ve olmayan hastalarda kahverengi yağ dokusu (KYD) aktivitesinin kıyaslanmasını amaçladık.
Gereç ve Yöntemler: Ocak 2014-Şubat 2018 tarihleri arasında kliniğimizde tüm vücut 18F-FDG PET/BT çekilen hastaların raporları hastane kayıtlarından araştırıldı. Yaş, cinsiyet, vücut kitle indeksi (VKİ), kan glukoz, bilirubin, total kolesterol (T-kol), düşük dansiteli lipoprotein (LDL) ve trigliserit (TG) düzeyleri not edildi. PET/BT görüntülemesi sırasında ortalama dış mekan hava sıcaklığı internetten araştırıldı. Tanı ve PET/BT sırasında hastalık aktivitesi hastane kayıtlarından araştrıldı. Standardize uptake değeri (SUV) ve kahverengi yağ dokusu volümü (KYV) PET/BT görüntülerinden hesaplandı. Ek olarak hepatic atenüasyon indeksi ve subkutan yağ dokusu kalınlığı (SKYDK) BT görüntülerinden hesaplandı. Aktif kanseri olan ve olmayan gruplar arasında median SUV ve KYV farkları analiz edildi.
Bulgular: Çeşitli onkolojik endikasyonlarla 18F-FDG PET/BT çekilen toplam 78 hasta (54 K; 24 E; ortalama yaş 34.415.6) çalışmaya dahil edildi. Her hastanın PET/BT görüntülerinde farklı KYD tutulumu vardı. SUV, KYV ve SKYDK için median değerleri sırasıyla 8.0 (2.7-37.0), 26.9 (2.1- 116) cm3 and 15.0 (3.0- 46.0) mm olarak bulundu. Hepatosteatoz indeksi 56 hastada (%71) %0-5, 20 hastada (26%) %6-30 ve 2 hastada (3%) >%30 idi. 26 hastada (33%) PET/BT görüntüleme sırasında aktif hastalık mevcuttu. Kahverengi yağ dokusu parametrelerinin gruplar arasında dağılımının incelemesinde, aktif kanseri olan ve olmayan hastalarda median SUV (p=0.008) ve KYV (p=0.008) değerleri arasında anlamlı farklılık bulundu.
Sonuç: Kanser gelişimi ve progresyonununda kahverengi yağ dokusu aktivasyonunun muhtemel rolünü destekler nitelikte olmak üzere, aktif kanseri olan hastalarda, olmayanlara göre KYD aktivitesi daha yüksek görünmektedir.

Keywords

kahverengi yağ dokusu, poziton emisyon tomografi, fluorodeoksiglukoz F-18

References

• 1. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004; 84: 277–359.
• 2. Cypess AM, Lehman S, Williams G, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009; 360: 1509– 7.
• 3. Kajimura S, Saito M. A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis. Annu Rev Physiol 2014; 76: 225–49.
• 4. Ouellet V, Routhier-Labadie A, Bellemare W, et al. Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. J Clin Endocrinol Metab 2011; 96: 192–9.
• 5. Pfannenberg C, Werner MK, Ripkens S, et al. Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans. Diabetes 2010; 59: 1789–93.
• 6. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold- activated brown adipose tissue in healthy men. N Engl J Med 2009; 360: 1500–8.
• 7. Virtanen KA, Lidell ME, Orava J, et al. Functional brown adipose tissue in healthy adults. N Engl J Med 2009; 360: 1518–25.
• 8. Saito M, Okamatsu-Ogura Y, Matsushita M, et al. High incidence of meta- bolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 2009; 58: 1526–31.
• 9. Shellock FG, Riedinger MS, Fishbein MC. Brown adipose tissue in cancer patients: possible cause of cancer-induced cachexia. J Cancer Res Clin Oncol 1986; 111: 82-5.
• 10. Dirat B, Bochet L, Dabek M, et al. Cancer-associated adipocytes exhibit an activated phenotype and con- tribute to breast cancer invasion. Cancer Res. 2011; 71: 2455–65.
• 11. Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Power surge: supporting cells "fuel" cancer cell mitochondria. Cell Metab. 2012; 15: 4–5.
• 12. Smorlesi A, Frontini A, Giordano A, et al. The adipose organ: white-brown adipocyte plasticity and metabolic inflammation. Obes Rev 2012; 2: 83–96.
• 13. Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: is beige the new brown. Genes Dev 2013; 27: 234–50.
• 14. Berstein LM. Cancer and heterogeneity of obesity: a potential contribution of brown fat. Future Oncol 2012; 8: 1537–48.
• 15. Sinha G. Homing in on the fat and cancer connection. J Natl Cancer Inst 2012; 104: 966–7.
• 16. Cinti S, Cancello R, Zingaretti MC, et al. CL316,243 and cold stress induce heterogeneous expression of UCP1 mRNA and protein in rodent brown adipocytes. J Histochem Cytochem 2002; 50: 21–31.
• 17. Lim S, Honek J, Xue Y, Seki T, et al. Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice. Nat Protoc 2012; 7: 606–15.
• 18. Yeung HW, Grewal RK, Gonen M, et al. Patterns of 18 F-FDG uptake in adipose tissue and muscle: a potential source of false-positives for PET. J Nucl Med 2003; 44: 1789–96.
• 19. Cook GJ, Fogelman I, Maisey MN. Normal physiological and benign pathological variants of 18-fluoro-2-deoxyglucose positron-emission tomography scanning: potential for error in interpretation. Semin Nucl Med 1996; 26: 308–14.
• 20. Chen KY, Cypess AM, Laughlin MR, et al. Brown adipose reporting criteria in imaging studies (BARCIST 1.0): recommendations for standardized FDG-PET/ CT experiments in humans. Cell Metab. 2016; 24: 210–22.
• 21. Cao Q, Hersl J, La H, Smith M, et al. BMC Cancer. A pilot study of FDG PET/CT detects a link between brown adipose tissue and breast cancer. 2014; 14: 126
• 22. Bos SA, Gill CM, Martinez-Salazar EL, et al. Preliminary investigation of brown adipose tissue assessed by PET/CT and cancer activity. Skeletal Radiol. 2019; 48: 413-9.
• 23. Huang YC, Chen TB, Hsu CC, et al. The relationship between brown adipose tissue activity and neoplastic status: an (18)F-FDG PET/CT study in the tropics. Lipids Health Dis. 2011; 10-238
• 24. Calle EE, Rodriguez C, Walker-Thurmond K, et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003; 348: 1625–38.
• 25. Chen J. Multiple signal pathways in obesity-associated cancer. Obes Rev. 2011; 12: 1063–70.
• 26. Renehan AG, Tyson M, Egger M, et al. Body- mass index and incidence of cancer: a systematic review and meta- analysis of prospective observational studies. Lancet. 2008; 371: 569–78.
• 27. Barbatelli G, Murano I, Madsen L, et al. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab. 2010; 298: 1244–53.
• 28. Walden TB, Hansen IR, Timmons JA, et al. Recruited vs. nonrecruited molecular signatures of brown, "brite," and white adipose tissues. Am J Physiol Endocrinol Metab. 2012; 302: 19–31.
• 29. Cypess AM, White AP, Vernochet C, et al. Anatomical localization, gene expression profiling and func- tional characterization of adult human neck brown fat. Nat Med. 2013; 19: 635–9.
• 30. Wu J, Bostrom P, Sparks LM, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012; 150: 366–76.
• 31. Bostrom P, Wu J, Jedrychowski MP, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012; 481: 463–8.
• 32. Jones LP, Buelto D, Tago E, et al. Abnormal mammary adipose tissue environment of brca1 mutant mice show a persistent deposition of highly vascularized multilocular adipocytes. J Cancer Sci Ther. 2011(Suppl 2).
• 33. Tsoli M, Moore M, Burg D, et al. Activation of thermogenesis in brown adipose tissue and dysregu- lated lipid metabolism associated with cancer cachexia in mice. Cancer Res. 2012; 72: 4372–82.
• 34. Brooks SL, Neville AM, Rothwell NJ, et al. Sympathetic activation of brown-adipose-tissue thermogenesis in cachexia. Biosci Rep 1981; 1: 509-17.
• 35. Bing C, Brown M, King P, et al. Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia. Cancer Res 2000; 60: 2405-10.
• 36. Dahlman I, Mejhert N, Linder K, et al. Adipose tissue pathways involved in weight loss of cancer cachexia. Br J Cancer 2010; 102: 1541–8
• 37. Ryden M, Agustsson T, Laurencikiene J, et al. Lipolysis—not inflammation, cell death, or lipogenesis—is involved in adipose tissue loss in cancer cachexia. Cancer 2008; 113: 1695–1704.
• 38. Özcan-Ekşi EE, Kara M, Berikol G, et al. A new radiological index for the assessment of higher body fat status and lumbar spine degeneration. Skeletal Radiol. 2021 Nov 18.
• 39. Teli MR, James OF, Burt AD, Bennett MK, Day CP. The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology. 1995; 22: 1714-9.
• 40. Lee SS, Park SH, Kim HJ, et al. Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations. J Hepatol. 2010; 52: 579-85
• 41. Lazar MA. Developmental biology. How now, brown fat? Science 2008, 321:1048-1049.
• 42. Kvetnansky R, Sabban EL, Palkovits M. Catecholaminergic systems in stress: structural and molecular genetic approaches. Physiol Rev 2009; 89: 535-606.