¹⁸F-FDG PET/CT in the Diagnosis of Cervical Cancer

Positron emission tomography coupled with computed tomography (PET/CT) has proven to be highly informative in the diagnosis of various malignant tumours. PET/CT examination takes into account biological and morphological data, which allow accurate tumour localisation and full staging of the disease, respectively. Cervical cancer (CC) is one of the most common, high-mortality cancers in women. The effectiveness of CC treatment depends on early diagnosis, which is connected to the assessment of local tumour spread and metastatic lymph node involvement and to the  detection of disease recurrence. The aim of the study was to  analyse the possibility of using PET/CT with ¹⁸F-FDG for the diagnosis of CC and the evaluation of treatment effectiveness. Additionally, the study aimed to analyse the potential of using other radiopharmaceuticals as biomarkers for the assessment of tumour response. Cervical malignancies are characterised by high glycolytic activity, which explains the superiority of ¹⁸F-FDG PET/CT over other traditional imaging methods in comprehensive diagnosis of patients with CC and, especially, in detecting nodal involvement and distant metastases. Also, ¹⁸F-FDG PET/CT plays an important part in the assessment of treatment effectiveness in CC patients. Further development of ¹⁸F-FDG PET/CT potential in the visualisation of malignant cervical lesions is associated with investigating the possibilities of using other specific radiopharmaceuticals to obtain information about the biological processes that support tumour cell growth: metabolism, proliferative activity, and oxygenation.

1. Aksel EM. Statistics of malignant tumors of female reproductive system. Onkoginekologiya = Oncogynecology. 2012;(1):18–23 (In Russ.)

2. Koh WJ, Greer BE, Abu-Rustum NR, Apte SM, Campos SM, Cho KR, et al. Cervical cancer, version 2.2015. J Natl Compr Canc Netw. 2015;13(4):395–404. https://doi.org/10.6004/jnccn.2015.0055

3. Stanley M. Human papillomavirus vaccines versus cervical cancer screening. Clin Oncol (R Coll Radiol). 2008;20(6):388–94. https://doi.org/10.1016/j.clon.2008.04.006

4. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008; 58(2):71–96. https://doi.org/10.3322/CA.2007.0010

5. Grigsby PW. The prognostic value of PET and PET/CT in cervical cancer. Cancer Imaging. 2008;8(1):146–55. https://doi.org/10.1102/1470-7330.2008.0022

6. Liu B, Gao S, Li S. A comprehensive comparison of CT, MRI, positron emission tomography or positron emission tomography/CT, and diffusion weighted imaging-MRI for detecting the lymph nodes metastases in patients with cervical cancer: a meta-analysis based on 67 studies. Gynecol Obstet Invest. 2017;82(3):209–22. https://doi.org/10.1159/000456006

7. Salaün PY, Abgral R, Malard O, Querellou-Lefranc S, Quere G, Wartski M, et al. Good clinical practice recommendations for the use of PET/CT in oncology. Eur J Nucl Med Mol Imaging. 2020;47(1):28–50. https://doi.org/10.1007/s00259-019-04553-8

8. Unterrainer M, Eze C, Ilhan H, Marschner S, Roengvoraphoj O, Schmidt-Hegemann NS, et al. Recent advances of PET imaging in clinical radiation oncology. Radiat Oncol. 2020;15(1):88. https://doi.org/10.1186/s13014-020-01519-1

9. Zytoon AA, Elsayed EE, Nassar AI, Koji M. Pivotal role of PET/CT in characterization of occult metastasis with undetermined origin. Egypt J Radiol Nucl Med. 2020;51: 240. https://doi.org/10.1186/s43055-020-00357-1

10. Jadvar H, Colletti PM, Delgado-Bolton R, Esposito G, Krause BJ, Iagaru AH, et al. Appropriate use criteria for ¹⁸F-FDG PET/CT in restaging and treatment response assessment of malignant disease. J Nucl Med. 2017;58(12):2026–37. https://doi.org/10.2967/jnumed.117.197988

11. Shahhosseini S. PET Radiopharmaceuticals. Iran J Pharm Res. 2011;10(1):1–2. https://doi.org/10.22037/ijpr.2010.890

12. Rajendran J, Mankoff D. Positron emission tomography imaging of hypoxia and blood flow in tumors. Cancer Drug Discovery and Development. In Vivo Imaging of Cancer Therapy. 2006;(4):47–71.

13. Lewis JS, Laforest R, Dehdashti F, Grigsby PW, Welch MJ, Siegel BA. An imaging comparison of ⁶⁴Cu-ATSM and ⁶⁰Cu-ATSM in cancer of the uterine cervix. J Nucl Med. 2008;49(7):1177–82. https://doi.org/10.2967/jnumed.108.051326

14. Wadsak W, Mitterhauser M. Basics and principles of radiopharmaceuticals for PET/CT. Eur J Radiol. 2010;73(3): 461–9. https://doi.org/10.1016/j.ejrad.2009.12.022

15. Yen TC, See LC, Lai CH, Yah-Huei CW, Ng KK, Ma SY, et al. 18F-FDG uptake in squamous cell carcinoma of the cervix is correlated with glucose transporter 1 expression. J Nucl Med. 2004;45(1):22–9. PMID:14734665

16. Rudlowski C, Becker AJ, Schroder W, Rath W, Büttner R, Moser M. GLUT1 messenger RNA and protein induction relates to the malignant transformation of cervical cancer. Am J Clin Pathol. 2003;120(5):691–8. https://doi.org/10.1309/4KYN-QM58-62JW-2GD7

17. Bar JK, Harłozińska A, Sedlaczek P, Kasiak J, Markowska J. Relations between the expression of p53, c-erbB-2, Ki-67 and HPV infection in cervical carcinomas and cervical dysplasias. Anticancer Res. 2001;21(2A):1001–6. PMID: 11396132

18. Boellaard R, Oyen WJ, Hoekstra CJ, Hoekstra OS, Visser EP, Willemsen AT, et al. The Netherlands protocol for standardisation and quantification of FDG whole body PET studies in multi-centre trials. Eur J Nucl Med Mol Imaging. 2008;35(12):2320–33. https://doi.org/10.1007/s00259-008-0874-2

19. Boellaard R, O’Doherty MJ, Weber WA, Mottaghy FM, Lonsdale MN, Stroobants SG, et al. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2010;37(1):181–200. https://doi.org/10.1007/s00259-009-1297-4

20. Herrera F, Prior J. The role of PET/CT in cervical cancer. Front Oncol. 2013;3:34. https://doi.org/10.3389/fonc.2013.00034

21. Mirpour S, Mhlanga J, Logeswaran P, Russo G, Mercier G, Subramaniam RM. The role of PET/CT in the management of cervical cancer. AJR Am J Roentgenol. 2013; 201(2):W192–205. https://doi.org/10.2214/ajr.12.9830

22. Peters WA, Liu PY, Barrett RJ, Stock RJ, Monk BJ, Berek JS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000;18(8):1606–13. https://doi.org/10.1200/JCO.2000.18.8.1606

23. Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: A Gynecologic Oncology Group Study. Gynecol Oncol. 1999;73(2):177–83. https://doi.org/10.1006/gyno.1999.5387

24. Nogami Y, Iida M, Banno K, Kisu I, Adachi M, Nakamura K, et al. Application of FDG-PET in cervical cancer and endometrial cancer: utility and future prospects. Anticancer Res. 2014;34(2):585–92. PMID:24510987

25. Mirpour S, Mhlanga JC, Logeswaran P, Russo G, Mercier G, Subramaniam RM. The role of PET/CT in the management of cervical cancer. AJR Am J Roentgenol. 2013;201(2):W192–205. https://doi.org/10.2214/AJR.12.9830

26. Ruan J, Zhang Y, Ren H. Meta-analysis of PET/CT detect lymph nodes metastases of cervical cancer. Open Med (Wars). 2018;13:436–42. https://doi.org/10.1515/med-2018-0065

27. Wright JD, Dehdashti F, Herzog TJ, Mutch DG, Huettner PC, Rader JS, et al. Preoperative lymph node staging of early-stage cervical carcinoma by [¹⁸F]-fluoro-2-deoxy-D-glucose-positron emission tomography. Cancer. 2005;104(11):2484–91. https://doi.org/10.1002/cncr.21527

28. Magné N, Chargari C, Vicenzi L, Gillion N, Messai T, Magné J, et al. New trends in the evaluation and treatment of cervix cancer: the role of FDG-PET. Cancer Treat Rev. 2008;34(8):671–81. https://doi.org/10.1016/j.ctrv.2008.08.003

29. Wong TZ, Jones EL, Coleman RE. Positron emission tomography with 2-deoxy-2-[¹⁸F]fluoro-Dglucose for evaluating local and distant disease in patients with cervical cancer. Mol Imaging Biol. 2004;6(1):55–62. https://doi.org/10.1016/j.mibio.2003.12.004

30. Tran BN, Grigsby PW, Dehdashti F, Herzog TJ, Siegel BA. Occult supraclavicular lymph node metastasis identified by FDG-PET in patients with carcinoma of the uterine cervix. Gynecol Oncol. 2003;90(3):572–6. https://doi.org/10.1016/s0090-8258(03)00402-5

31. Loft A, Berthelsen AK, Roed H, Ottosen C, Lundvall L, Knudsen J, et al. The diagnostic value of PET/CT scanning in patients with cervical cancer: a prospective study. Gynecol Oncol. 2007;106(1):29–34. https://doi.org/10.1016/j.ygyno.2007.03.027

32. Wang X, Koch S. Positron emission tomography/computed tomography potential pitfalls and artifacts. Curr Probl Diagn Radiol. 2009;38(4):156–69. https://doi.org/10.1067/j.cpradiol.2008.01.001

33. Amit A, Person O, Keidar Z. FDG PET/CT in monitoring response to treatment in gynecological malignancies. Curr Opin Obstet Gynecol. 2013;25(1):17–22. https://doi.org/10.1097/GCO.0b013e32835a7e96

34. Schwarz JK, Grigsby PW, Dehdashti F, Delbeke D. The role of 18F-FDG PET in assessing therapy response in cancer of the cervix and ovaries. J Nucl Med. 2009;50(Suppl 1):64S–73S. https://doi.org/10.2967/jnumed.108.057257

35. Grigsby PW, Siegel BA, Dehdashti F, Rader J, Zoberi I. Posttherapy [¹⁸F] fluorodeoxyglucose positron emission tomography in carcinoma of the cervix: response and outcome. J Clin Oncol. 2004;22(11):2167–71. https://doi.org/10.1200/JCO.2004.09.035

36. Chu Y, Zheng A, Wang F, Lin W, Yang X, Han L, et al. Diagnostic value of 18F-FDG-PET or PET-CT in recurrent cervical cancer: a systematic review and meta-analysis. Nucl Med Commun. 2014;35(2):144–50. https://doi.org/10.1097/MNM.0000000000000026

37. Brooks RA, Rader JS, Dehdashti F, Mutch DG, Powell MA, Thaker PH, et al. Surveillance FDG-PET detection of asymptomatic recurrences in patients with cervical cancer. Gynecol Oncol. 2009;112(1):104–9. https://doi.org/10.1016/j.ygyno.2008.08.028

38. Emami NA, Najafgholian S, Rostami A, Sistani A, Shojaeifar S, Esparvarinha M, et al. The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment. Cancer Cell Int. 2021;21(1):62. https://doi.org/10.1186/s12935-020-01719-5

39. Nordsmark M, Loncaster J, Aquino-Parsons C, Chou SC, Gebski V, West C, et al. The prognostic value of pimonidazole and tumour pO2 in human cervix carcinomas after radiation therapy: a prospective international multi-center study. Radiother Oncol. 2006;80(2):123–31. https://doi.org/10.1016/j.radonc.2006.07.010

40. Pinker K, Andrzejewski P, Baltzer P, Polanec SH, Sturdza A, Georg D, et al. Multiparametric [¹⁸F] fluorodeoxyglucose/[¹⁸F]fluoromisonidazole positron emission tomography/magnetic resonance imaging of locally advanced cervical cancer for the non-invasive detection of tumor heterogeneity: a pilot study. PLoS One. 2016;11(5):e0155333. https://doi.org/10.1371/journal.pone.0155333