The female gonad, ovary, is a paired intraperitoneal endocrine organ, located on either side of the uterus. Ovaries are attached to fimbria, which connects them to the fallopian tubes. Posterior to the ovaries are the ureters and internal iliac arteries. The ovary has dual blood supply from the ovarian artery and uterine artery, and the arteries may make an anastomosis with each other. The left ovarian vein empties into left renal vein, and the right ovarian vein into the inferior vena cava.
The size of normal ovary is 2.0 × 3.5 × 1.0 cm, but its size changes with age: it is at its largest, ∼ 7.7 mL, at the age of 20, and at menopause the average volume is ∼2.8 mL (Zhu et al., 2016). Below the outer (germinal) epithelium of the ovary and connective tissue (tunica albuginea) is the ovarian cortex, containing follicles of different sizes (<9 mm) and maturity. Inside the cortex resides ovarian medulla and hilus, containing blood vessels and connective tissue.
Ovarian follicles secrete hormones from their granulosa and theca cells, including estrogen, testosterone, and progesterone. Hypotalamus releases GnRH, which causes the anterior pituitary to release FSH and LH. FSH affects granulosa cells and LH the theka cells, inducing production of progesterone and estrogen which prepare the uterus for menstruation. Granulosa cells promote follicle growth and maturation. Follicles enlarge during menstrual cycle, until a dominant follicle is formed and other follicles degenerate. From a matured follicle, an oocyte is expelled through fallopian tubes into the uterus. In the place of the oocyte, a temporary endocrine organ corpus luteum secretes progesterone and estradiol to delay the start of menstruation. Inhibin is secreted by corpus luteum for signalling to the pituitary to inhibit FSH secretion. Without fertilization, corpus luteum will degenerate into corpus albicans.
During the menopause the estrogen production is rapidly decreased. Decreased estrogen decreases the activity of osteoblasts, leading to bone loss. Estrogen replacement therapy can protect the bone mass.
Ovarian cysts are very common. Cysts are fluid-filled sacks of variable size, and are usually harmless. Polycystic ovary syndrome (PCOS) is linked to hyperandrogenism.
Ovarian cancer is relatively rare, but since it is usually symptomless or symptoms are nonspecific in the early phases, it is usually diagnosed in advanced stage, when it has poor prognosis and a high recurrence rate. Therefore ovarian cancer is the leading cause of death from gynecologic cancer. Most malignant ovarian tumours are epithelial ovarian cancers (EOC), including many histopathologically different tumours. Ovarian cancer has distinct type of disease spread in abdomen and above diaphragm.
Most ovarian cancer patients do not benefit from anti-estrogen therapies, and development of resistance to endocrine treatment is common problem. Expression of HER2 is associated with an advanced stage of ovarian cancer and higher recurrence rate. HER2-overexpressing cancer can be treated with for example trastuzumab and lapatinib. Patients for HER2-targeted therapy can be selected using specific PET radioligands (Keyaerts et al., 2016).
FDG PET is not optimal for detecting ovarian cancer, because different ovarian cancer subtypes have different FDG avidity, while FDG uptake in many normal abdominal structures is high (Kemppainen et al., 2019). Ovarian FDG uptake can be high during late follicular to early luteal phase of the menstrual cycle, but in menopausal women FDG uptake is low in normal ovaries and uterus (Lerman et al., 2004; Nishizawa et al., 2005). FDG PET may still be useful in diagnosis of ovarian cancer in postmenopausal women (Khiewvan et al., 2017), detecting metastases (Han et al., 2018), and in assessment of treatment response (Takeuchi et al., 2014; Vallius et al., 2018; Watanabe et al., 2019). In complete responders a routine follow-up FDG PET is not recommended (Hynninen et al., 2018).
Ovarian cancers with cyclooxygenase-1 (COX-1) overexpression are associated with a poor prognosis, tumorigenesis, and tumor invasion. [11C]PS13 is a COX-1 targeting PET radioligand, which is used for studying neuroinflammation but may be useful for ovarian cancer imaging (Boyle et al., 2021).
Estrogen receptor (ER) expression can be assessed using PET radiopharmaceuticals such as 16α-[18F]fluoro-17β-estradiol ([18F]FES). [18F]FES can detect changes in ER expression, induced by HER2-targeted treatment (Antunes et al., 2020).
Endometrial cancer ("uterine cancer") is common cancer in women. It begins in the lining (endometrium) of the uterus. Uterine sarcoma and other uterine cancers are rare compared to endometrial cancer.
There is no aromatase activity in healthy uterine tissue, but in endometrial cancer and other uterine diseases aromatase activity has been observed. PET with estrogen receptor radioligand [18F]FES could be used for assessing ERα distribution and treatment planning (Tsujikawa et al., 2011; Yamada et al., 2021).
Cervical cancer occurs in the cells of cervix, the lower part of uterus. Most cases of cervical cancer are caused by human papillomavirus (HPV) infection, and could be prevented with vaccination.
Delgado Bolton RC, Aide N, Colletti PM, Ferrero A, Paez D, Skanjeti A, Giammarile F. EANM guideline on the role of 2-[18F]FDG PET/CT in diagnosis, staging, prognostic value, therapy assessment and restaging of ovarian cancer, endorsed by the American College of Nuclear Medicine (ACNM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the International Atomic Energy Agency (IAEA). Eur J Nucl Med Mol Imaging 2021; 48: 3286-3302. doi: 10.1007/s00259-021-05450-9.
Gibson E, Mahdy H. Anatomy, Abdomen and Pelvis, Ovary. In: StatPearls. StatPearls Publishing, Treasure Island (FL); 2019. NBK545187.
Khiewvan B, Torigian DA, Emamzadehfard S, Paydary K, Salavati A, Houshmand S, Werner TJ, Alavi A. An update on the role of PET/CT and PET/MRI in ovarian cancer. Eur J Nucl Med Mol Imaging 2017; 44: 1079-1091. doi: 10.1007/s00259-017-3638-z.
Mironov S, Akin O, Pandit-Taskar N, Hann LE. Ovarian cancer. Radiol Clin North Am. 2007; 45(1): 149-166. doi: 10.1016/j.rcl.2006.10.012.
Ponisio MR, Dehdashti F. A role of PET agents beyond FDG in gynecology. Semin Nucl Med. 2019; 49(6): 501-511. doi: 10.1053/j.semnuclmed.2019.06.008.
Sharma SK, Nemieboka B, Sala E, Lewis JS, Zeglis BM. Molecular imaging of ovarian cancer. J Nucl Med. 2016; 57: 827-833. doi: 10.2967/jnumed.115.172023.
Updated at: 2023-01-08
Created at: 2020-01-23
Written by: Vesa Oikonen