11C-methionine PET aids localization of microprolactinomas in patients with intolerance or resistance to dopamine agonist therapy

Abstract

Purpose: To assess the potential for ¹¹C-methionine PET (Met-PET) coregistered with volumetric magnetic resonance imaging (Met-PET/MR^CR) to inform clinical decision making in patients with poorly visualized or occult microprolactinomas and dopamine agonist intolerance or resistance.

Patients and methods: Thirteen patients with pituitary microprolactinomas, and who were intolerant (n = 11) or resistant (n = 2) to dopamine agonist therapy, were referred to our specialist pituitary centre for Met-PET/MR^CR between 2016 and 2020. All patients had persistent hyperprolactinemia and were being considered for surgical intervention, but standard clinical MRI had shown either no visible adenoma or equivocal appearances.

Results: In all 13 patients Met-PET/MR^CR demonstrated a single focus of avid tracer uptake. This was localized either to the right or left side of the sella in 12 subjects. In one patient, who had previously undergone surgery for a left-sided adenoma, recurrent tumor was unexpectedly identified in the left cavernous sinus. Five patients underwent endoscopic transsphenoidal selective adenomectomy, with subsequent complete remission of hyperprolactinaemia and normalization of other pituitary function; three patients are awaiting surgery. In the patient with inoperable cavernous sinus disease PET-guided stereotactic radiosurgery (SRS) was performed with subsequent near-normalization of serum prolactin. Two patients elected for a further trial of medical therapy, while two declined surgery or radiotherapy and chose to remain off medical treatment.

Conclusions: In patients with dopamine agonist intolerance or resistance, and indeterminate pituitary MRI, molecular (functional) imaging with Met-PET/MR^CR can allow precise localization of a microprolactinoma to facilitate selective surgical adenomectomy or SRS.

Keywords: 11C-methionine PET; Dopamine agonist intolerance/ resistance; Microprolactinoma.

Fig. 1

Schematic representation of the clinical courses for each of the thirteen patients prior to and following Met-PET. DA dopamine agonist, Met-PET/MR^{CR 11}C-methionine PET coregistered with volumetric (FSPGR) MRI, PET Positron Emission Tomography, PRL prolactin, SRS stereotactic radiosurgery, TSS transsphenoidal surgery, ULN upper limit of normal

Fig. 2

MRI and Met-PET findings with 3D reconstruction of the sella and parasellar regions in case 1. A–B Pre- and post-contrast coronal T1 SE MRI demonstrates equivocal appearances, with two possible areas of reduced enhancement (arrows). C Met-PET/MR^CR reveals avid focal tracer uptake in the left side of the gland adjacent to the cavernous sinus (arrow). D–I 3D reconstructed images, combining PET, CT and FSPGR MRI datasets, allows appreciation of the location of the tumor (yellow) with respect to the normal gland (turquoise) and proximity of the tumor to key adjacent structures including the intracavernous cartoid artery (red). At transsphenoidal surgery, a microadenoma abutting the left cavernous sinus was resected and confirmed histologically to be a prolactinoma. Postoperatively the patient remains normoprolactinemic and eupituitary. CT computed tomography, FSPGR fast spoiled gradient recalled echo, Gad gadolinium, MRI magnetic resonance imaging, Met-PET/MR^{CR 11}C-methionine PET-CT coregistered with volumetric (FSPGR) MRI, PET positron emission tomography, SE spin echo

Fig. 3

MRI and Met-PET findings in cases 2, 3, 4 and 8. A–H Pre- and post-contrast coronal T1 SE MRI show equivocal appearances in four patients, identifying either no abnormality or possible single or multiple lesions (arrows). I–L In contrast, in all four subjects Met-PET/MR^CR demonstrates a single focus of intense tracer uptake which was subsequently confirmed at transsphenoidal surgery to be the site of a microprolactinoma. Postoperatively, all patients remain normoprolactinemic and eupituitary. FSPGR fast spoiled gradient recalled echo, Gad gadolinium, MRI magnetic resonance imaging, Met-PET/MR^{CR 11}C-methionine PET-CT coregistered with volumetric (FSPGR) or SE MRI, PET positron emission tomography, SE spin echo

Fig. 4

PET–guided stereotactic radiosurgery in case 10. A–B Post-contrast coronal T1 SE and FSPGR MRI demonstrate indeterminate appearances in a patient who had previously undergone transsphenoidal surgery for a left-sided microprolactinoma. C Axial FSPGR MRI shows possible recurrent tumor in the left cavernous sinus (yellow arrow). D–E Coronal and axial Met-PET/MR^CR confirm avid tracer uptake at the site of the suspected recurrence (yellow arrow); tracer uptake within the remaining normal gland is also seen (white arrow). F Treatment plan for PET-guided SRS. Three years later serum prolactin was near-normalized (1.4 × ULN). FSPGR fast spoiled gradient recalled echo, Gad gadolinium, MRI magnetic resonance imaging, Met-PET/MR^{CR 11}C-methionine PET-CT coregistered with volumetric (FSPGR) MRI, PET positron emission tomography, PTV Planning Target Volume, SE spin echo, ULN upper limit of normal