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. 2012 Jul;85(1015):1020–1024. doi: 10.1259/bjr/26645378

Oestrogen-related tumour phenotype: positron emission tomography characterisation with 18F-FDG and 18F-FES

T Tsujikawa 1,2, Y Yoshida 3, H Maeda 4, T Tsuchida 2, T Mori 1, Y Kiyono 1, H Kimura 2, H Okazawa 1
PMCID: PMC3474065  PMID: 22337690

Abstract

This article outlines the role of 16α-[18F]fluoro-17β-oestradiol (18F-FES) positron emission tomography (PET) combined with 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) in patients with oestrogen-related tumours for evaluating tumour phenotype. 18F-FES-PET combined with 18F-FDG is helpful in characterising the distinct phenotypic features of oestrogen-related tumours; that is, inter- and intrapatient tumour heterogeneity, which indicates its great potential as a determinant of individualised treatment and a prognostic predictor for patients with oestrogen-related tumours.

Breast cancer was the most common female malignancy newly diagnosed in the UK in 2008 (n = 47 693), and endometrial cancer was the most commonly diagnosed gynaecological malignancy affecting UK females in 2007 (n = 7536) [1]. In the past few decades, positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) has been used for diagnosis of breast cancer and gynaecological malignancies and is considered to be superior to conventional imaging methods in diagnostic accuracy for detecting metastatic lesions and local recurrence [2-5]. FDG-PET can also be useful in evaluating the response of metastatic breast cancer to systematic therapy [2,3]. On the other hand, both breast and endometrial cancer are oestrogen-related tumours for which oestrogen is critical for their development and progression. 16α-[18F]fluoro-17β-oestradiol (18F-FES) is an 18F-labelled compound of oestradiol, the most bioactive type of oestrogen, and 18F-FES-PET has been well established for diagnosis, staging and post-therapeutic follow-up in patients with oestrogen receptor (ER)-positive breast cancer [6-11]. In particular, the ER status is the most important determinant of response to endocrine therapy in breast cancer patients. Compared with an in vitro assay of tumour biopsy material, PET imaging has the advantage of being able to measure in vivo tumour behaviour, characterise the entire tumour burden and capture the heterogeneity of the tumour phenotype [12,13]. Recently, we applied 18F-FES-PET imaging to the diagnosis of gynaecological tumours [14-19] and showed in particular that the uptake value of 18F-FES combined with 18F-FDG is associated with tumour aggressiveness in endometrial cancer; that is, endometrial carcinoma reduces oestrogen dependency with increased glucose metabolism as it progresses to a higher stage or grade, and the 18F-FDG:18F-FES uptake ratio is the most informative index reflecting tumour aggressiveness [17]. An imaging study combining 18F-FES and 18F-FDG-PET has the potential to characterise in vivo oestrogen-related tumour phenotypes. In this article, we review oestrogen-related tumour phenotyping by 18F-FDG-PET and illustrate the role of 18F-FES-PET combined with 18F-FDG by showing representative cases.

Tumour phenotyping by 18F-FDG-PET

Several recent investigations reported the ability of 18F-FDG-PET to characterise breast cancer tumour phenotype. They indicated that enhanced tumour 18F-FDG uptake significantly correlates with ER negativity as a whole [20-24]. The latest report by Groheux et al [24] showed that 18F-FDG uptake is highest in patients with poor prognostic features (high grade, hormone receptor negativity, triple negativity, metaplastic tumours). As for endometrial cancer, our recent study with a small sample size (n = 19) did not show a significant correlation between tumour 18F-FDG uptake and hormone receptor expression [18]. However, a recent report showed that 18F-FDG accumulation by a primary endometrial cancer tumour significantly correlated with the differentiation grade, which still applies to the revised International Federation of Gynecology and Obstetrics staging classification 2009 [25]. Molecular imaging, including 18F-FDG-PET, which has hitherto been used mainly for tumour detection and staging, can play an important role in measuring tumour phenotype [13].

Tumour phenotyping by 18F-FES-PET combined with 18F-FDG

In this section we illustrate the role of 18F-ES-PET combined with 18F-DG for oestrogen-related tumour phenotyping by showing representative cases.

Case 1

A 78-year-old female was hospitalised with suspected endometrial cancer and lung metastases. Endometrial biopsy revealed the uterine tumour to be grade II endometrioid adenocarcinoma, and pelvic MRI indicated myometrial invasion. The patient underwent 18F-ES-PET scan for evaluation of ER density and 18F-FDG-PET scan to detect other metastatic lesions. PET images showed significantly higher accumulation of 18F-FDG [standardised uptake value (SUV) mean, 9.5] than 18F-FES (SUV mean, 1.7) in the primary tumour (Figure 1). Although right and left lung tumours showed intense accumulation of 18F-FDG (SUV mean, 10.1 and 5.7, respectively), almost no 18F-FES accumulation was detected visually and uptake values of 18F-FES were not measurable in the lung tumours. The 18F-FDG:18F-FES SUV ratio was 5.6 in the primary tumour, whereas somewhat higher 18F-FES uptake (SUV mean, 1.8) than 18F-FDG uptake (SUV mean, 1.1) was incidentally detected in the left breast. This was determined to be invasive ductal carcinoma by subsequent aspiration cytology (Figure 1). The 18F-FDG:18F-FES SUV ratio was 0.6 in the breast tumour.

Figure 1.

Figure 1

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A 78-year-old female with advanced endometrial cancer and early-stage breast cancer. Maximum-intensity projection positron emission tomography (PET) images with (a) 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) and (b) 16α-[18F]fluoro-17β-oestradiol (18F-FES) demonstrated significantly higher accumulation of 18F-FDG [standardised uptake value (SUV) mean, 9.5] than 18F-FES (SUV mean, 1.7) in the primary uterine tumour (arrows). Although right and left lung tumours showed intense accumulation of 18F-FDG (SUV mean, 10.1 and 5.7, respectively), almost no 18F-FES accumulation was visually detected. The 18F-FDG:18F-FES SUV ratio was 5.6 in the primary tumour, whereas somewhat higher 18F-FES uptake (SUV mean, 1.8) than 18F-FDG uptake (SUV mean, 1.1) was incidentally detected in the left breast (arrowheads). This was determined as invasive ductal carcinoma by subsequent aspiration cytology. The 18F-FDG:18F-FES ratio was 0.6 in the breast tumour. (c) Transaxial contrast-enhanced T1 weighted MRI, (d) 18F-FDG and (e) 18F-FES-PET images of the primary endometrial cancer arrows. Transaxial CT (f and h) and 18F-FDG-PET (g and i) images of right and left lung tumours (arrows), respectively. Transaxial CT (j), 18F-FDG (k) and 18F-FES-PET (l) images of left breast cancer (arrow heads).

In this case of oestrogen-related tumours derived from two different organs, tracer accumulation patterns of 18F-FES and 18F-FDG were completely different between advanced endometrial cancer (18F-FDG:18F-FES ratio, 5.6 in the primary tumour) and early-stage breast cancer (18F-FDG:18F-FES ratio, 0.6). Although the patient was followed up without treatment by choice, multiple bone and liver metastases appeared besides the progression of the primary tumour and she died within 1 year of the initial visit. During that time, no tendency for increased size was observed in the left breast tumour. Based on the opposite tracer accumulation pattern, combined 18F-FES and 18F-FDG-PET scan was considered a useful tool, providing supplementary information for in vivo phenotyping of two different oestrogen-related tumours.

Case 2

In patients with multiple metastases from breast cancer, the combination of 18F-FES and 18F-FDG-PET imaging studies has the potential to reflect tumour heterogeneity and characterise the in vivo tumour phenotype. A 64-year-old female with multiple metastases from breast cancer showed almost the same degree of accumulation of 18F-FDG (SUV mean, 4.8) as 18F-FES (SUV mean, 4.7) in left hilar lymphadenopathy, whereas higher 18F-FES uptake (SUV mean, 3.2) than 18F-FDG uptake (SUV mean, 1.3) was detected in right supraclavicular lymphadenopathy (Figure 2). The 18F-FDG:18F-FES SUV ratio was 1.0 and 0.4 in left hilar and right supraclavicular lymphadenopathy, respectively.

Figure 2.

Figure 2

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A 64-year-old female with multiple metastases from breast cancer. Maximum-intensity projection positron emission tomography images with (a) 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) and (b) 16α-[18F]fluoro-17β-oestradiol (18F-FES) demonstrated almost the same degree of accumulation of 18F-FDG [standardised uptake value (SUV) mean, 4.8] as 18F-FES (SUV mean, 4.7) in left hilar lymphadenopathy (arrows), whereas higher 18F-FES uptake (SUV mean, 3.2) than 18F-FDG uptake (SUV mean, 1.3) was detected in right supraclavicular lymphadenopathy (arrowheads). The 18F-FDG:18F-FES SUV ratio was 1.0 and 0.4 in left hilar and right supraclavicular lymphadenopathy, respectively.

We previously reported that the 18F-FDG:18F-FES SUV ratio is the most informative index reflecting tumour aggressiveness in patients with endometrial cancer [17], which may also be applied to patients with other oestrogen-related tumours such as multiple metastases from breast cancer. The index of the 18F-FDG:18F-FES SUV ratio has the advantage of being able to cancel out the partial volume effect, which greatly influences the interpretation of tracer uptake by a lesion. In addition, the ratio could be used as a determinant of hormonal therapies such as tamoxifen and aromatase inhibitor for breast cancer and progestational agents and gonadotropin-releasing hormone agonists for gynaecological tumours. In fact, hormonal treatment was not effective in this case and the patient died of carcinomatous pleuritis; nevertheless, an optimal range of the ratio for prediction of therapeutic efficacy may exist. Future prospective studies with large sample sizes are required to prove the benefit of a combination of 18F-FES and 18F-FDG-PET imaging.

Conclusion

The combination of molecular imaging studies has considerable potential for in vivo tumour phenotyping, which helps move towards better and more individualised cancer treatment. As Mankoff and Dehdashti [13] put it, “1 plus 1 is more than 2”.

References

  • 1.info. cancerresearchuk.org [homepage on the internet] London, UK: Cancer Research UK; 2008. Available from: http://info.cancerresearchuk.org/ [Google Scholar]
  • 2.Rosen EL, Eubank WB, Mankoff DA. FDG PET, PET/CT, and breast cancer imaging. Radiographics 2007;27:S215–29 [DOI] [PubMed] [Google Scholar]
  • 3.Oude Munnink TH, Nagengast WB, Brouwers AH, Schröder CP, Hospers GA, Lub-de Hooge MN, et al. Molecular imaging of breast cancer. Breast 2009;18:S66–73 [DOI] [PubMed] [Google Scholar]
  • 4.Grigsby PW. Role of PET in gynecologic malignancy. Curr Opin Oncol 2009;21:420–4 [DOI] [PubMed] [Google Scholar]
  • 5.Basu S, Li G, Alavi A. PET and PET-CT imaging of gynecological malignancies: present role and future promise. Expert Rev Anticancer Ther 2009;9:75–96 [DOI] [PubMed] [Google Scholar]
  • 6.McGuire AH, Dehdashti F, Siegel BA, Lyss AP, Brodack JW, Mathias CJ, et al. Positron tomographic assessment of 16α-[18F]fluoro-17β-estradiol uptake in metastatic breast carcinoma. J Nucl Med 1991;32:1526–31 [PubMed] [Google Scholar]
  • 7.Dehdashti F, Mortimer JE, Siegel BA, Griffeth LK, Bonasera TJ, Fusselman MJ, et al. Positron tomographic assessment of estrogen receptors in breast cancer: comparison with FDG-PET and in vitro receptor assays. J Nucl Med 1995;36:1766–74 [PubMed] [Google Scholar]
  • 8.Dehdashti F, Flanagan FL, Mortimer JE, Katzenellenbogen JA, Welch MJ, Siegel BA. Positron emission tomographic assessment of “metabolic flare” to predict response of metastatic breast cancer to antiestrogen therapy. Eur J Nucl Med 1999;26:51–6 [DOI] [PubMed] [Google Scholar]
  • 9.Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol 2001;19:2797–803 [DOI] [PubMed] [Google Scholar]
  • 10.Linden HM, Stekhova SA, Link JM, Gralow JR, Livingston RB, Ellis GK, et al. Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment in breast cancer. J Clin Oncol 2006;24:2793–9 [DOI] [PubMed] [Google Scholar]
  • 11.Sundararajan L, Linden HM, Link JM, Krohn KA, Mankoff DA. 18F-Fluoroestradiol. Semin Nucl Med 2007;37:470–6 [DOI] [PubMed] [Google Scholar]
  • 12.Mankoff DA, Link JM, Linden HM, Sundararajan L, Krohn KA. Tumor receptor imaging. J Nucl Med 2008;49:149S–63S [DOI] [PubMed] [Google Scholar]
  • 13.Mankoff DA, Dehdashti F. Imaging tumor phenotype: 1 plus 1 is more than 2. J Nucl Med 2009;50:1567–9 [DOI] [PubMed] [Google Scholar]
  • 14.Tsuchida T, Okazawa H, Mori T, Kobayashi M, Yoshida Y, Fujibayashi Y, et al. In vivo imaging of estrogen receptor concentration in the endometrium and myometrium using FES PET—influence of menstrual cycle and endogenous estrogen level. Nucl Med Biol 2007;34:205–10 [DOI] [PubMed] [Google Scholar]
  • 15.Yoshida Y, Kurokawa T, Sawamura Y, Shinagawa A, Okazawa H, Fujibayashi Y, et al. The positron emission tomography with F18 17β-estradiol has the potential to benefit diagnosis and treatment of endometrial cancer. Gynecol Oncol 2007;104:764–6 [DOI] [PubMed] [Google Scholar]
  • 16.Tsujikawa T, Yoshida Y, Mori T, Kurokawa T, Fujibayashi Y, Kotsuji F, et al. Uterine tumors: pathophysiologic imaging with 16α-[18F]fluoro-17β-estradiol and 18F fluorodeoxyglucose PET—initial experience. Radiology 2008;248:599–605 [DOI] [PubMed] [Google Scholar]
  • 17.Tsujikawa T, Yoshida Y, Kudo T, Kiyono Y, Kurokawa T, Kobayashi M, et al. Functional images reflect aggressiveness of endometrial carcinoma: estrogen receptor expression combined with FDG-PET. J Nucl Med 2009;50:1598–604 [DOI] [PubMed] [Google Scholar]
  • 18.Tsujikawa T, Yoshida Y, Kiyono Y, Kurokawa T, Kudo T, Fujibayashi Y, et al. Functional oestrogen receptor α imaging in endometrial carcinoma using 16α-[18F]fluoro-17β-oestradiol PET. Eur J Nucl Med Mol Imaging 2011;38:37–45 [DOI] [PubMed] [Google Scholar]
  • 19.Yoshida Y, Kiyono Y, Tsujikawa T, Kurokawa T, Okazawa H, Kotsuji F. Additional value of 16α-[18F]fluoro-17β-oestradiol PET for differential diagnosis between uterine sarcoma and leiomyoma in patients with positive or equivocal findings on [18F]fluorodeoxyglucose PET. Eur J Nucl Med Mol Imaging 2011;38:1824–31 [DOI] [PubMed] [Google Scholar]
  • 20.Mavi A, Cermik TF, Urhan M, Puskulcu H, Basu S, Yu JQ, et al. The effects of estrogen, progesterone, and C-erbB-2 receptor states on 18F-FDG uptake of primary breast cancer lesions. J Nucl Med 2007;48:1266–72 [DOI] [PubMed] [Google Scholar]
  • 21.Basu S, Chen W, Tchou J, Mavi A, Cermik T, Czerniecki B, et al. Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization. Cancer 2008;112:995–1000 [DOI] [PubMed] [Google Scholar]
  • 22.Ueda S, Tsuda H, Asakawa H, Shigekawa T, Fukatsu K, Kondo N, et al. Clinicopathological and prognostic relevance of uptake level using 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in primary breast cancer. Jpn J Clin Oncol 2008;38:250–8 [DOI] [PubMed] [Google Scholar]
  • 23.Osborne JR, Port E, Gonen M, Doane A, Yeung H, Gerald W, et al. 18F-FDG PET of locally invasive breast cancer and association of estrogen receptor status with standardized uptake value: microarray and immunohistochemical analysis. J Nucl Med 2010;51:543–50 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Groheux D, Giacchetti S, Moretti JL, Porcher R, Espié M, Lehmann-Che J, et al. Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer. Eur J Nucl Med Mol Imaging 2011;38:426–35 [DOI] [PubMed] [Google Scholar]
  • 25.Nakamura K, Kodama J, Okumura Y, Hongo A, Kanazawa S, Hiramatsu Y. The SUVmax of 18F-FDG PET correlates with histological grade in endometrial cancer. Int J Gynecol Cancer 2010;20:110–5 [DOI] [PubMed] [Google Scholar]

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