Prolactinomas are well-differentiated tumors that originate from pituitary lactotroph cells, causing hyperprolactinemia and resulting in gonadal and sexual dysfunction [1, 2]. Prolactinomas comprise 50–60% of all pituitary neuroendocrine tumors, and occur most frequently in women aged 20–50 years [1, 2]. As the first-line treatment option, drug treatment for prolactinomas relies on the use of DAs, such as bromocriptine and cabergoline [2, 3]. The majority of patients treated with DAs have curative effects in normalizing prolactin levels and reducing tumor size [3]. However, some patients may require high doses or be resistant to medical therapy [3].
The dopamine receptor family is divided into five subtypes (dopamine receptor D1-5, DRD1-5) [4, 5]. DRD1, DRD2, DRD4 and DRD5 are expressed in normal human pituitary glands or pituitary neuroendocrine tumors, except DRD3 [6, 7]. Under normal circumstances, dopamine is implicated in activating DRD2 and inhibiting prolactin secretion by pituitary lactotroph cells [8]. DRD2 is also highly expressed in prolactinoma, which becomes a selective therapy target by DA [4, 5]. However, approximately 20–30% patients with prolactinomas are resistant to BRC and around 10–20% to CAB. DA resistance has been defined as a failure to achieve normal PRL levels together with a ≥ 50% reduction in tumor size at maximally tolerated doses. Generally, the effectiveness of BRC or CAB has been related to a decreased expression in DRD2, although other molecular mechanisms also underpin the DA resistance, such as abnormal expressed miRNAs, PRDM2, PRB3, etc [9, 10]. In other words, DRD2 density in prolactinomas may positively correlate with their clinical responsiveness to DA. However, the preclinical evaluation of DRD2 expression in prolactinomas is still rare.
Positron emission tomography (PET) is an effective imaging technique to study receptor distribution in the brains of live animals and humans. To date, PET studies in humans have been widely used to quantitatively analyze dopamine receptors in the central nervous system in vivo to diagnose and research a variety of neuropsychiatric diseases [11, 12]. However, dopaminergic imaging has rarely been studied in prolactinomas. Only 11C-N-methylspiperone, 11C-raclopride, 18F-FDOPA and 18F-fallypride as PET tracers have been used in prolactinomas [13–15]. Due to its convenience and stability, 18F-fallypride has recently been successfully tested as a PET tracer to study prolactinomas [15]. However, this study was performed using PET/CT which can not show the detailed anatomical characteristics when compared with PET/MR. In addition, 18F-fallypride PET/MR was not used to study prolactinomas.
In the present study, 18F-fallypride PET/MR was first used to study prolactinomas in humans. The aim of the study was to demonstrate whether DRD2 expression based on 18F-fallypride PET/MR could predict DA treatment resistance in prolactinomas.