Dopamine agonist therapy of clinically non-functioning pituitary macroadenomas. Is there a role for 123I-epidepride dopamine D2 receptor imaging?

Abstract

Objective: Clinically non-functioning pituitary adenomas (NFPAs) can express functional dopamine D2 receptors. Therapy with dopamine (DA) agonists may result in a NFPA size reduction. However, DA agonist-sensitive and -resistant NFPAs are clinically indistinguishable. We have studied the correlation between in vivo imaging of D2 receptors using 123 I-epidepride and the radiological response of NFPA to DA in 18 patients. Methods: Patients were treated with either cabergoline (1-2 mg/week) or quinagolide (150-300 mg/day) for a mean period of 89.7 months (range, 34-187 months). Results: Pituitary uptake of 123 I-epidepride varied from slight uptake classified as grade 0 to very high classified as grade 3. Grade 0 uptake was found in four patients; grade 1 in three; grade 2 in ten, and grade 3 in one. NFPA stabilization or shrinkage with DA agonist therapy showed no significant difference between grade 0, 1, and 2 tumors (mean tumor stabilization or shrinkage: 31, 30, and 36% respectively). However, when we considered a decrease in tumor size ranging from 0 to 20% as tumor stabilization and O20% decrease in tumor size as true shrinkage, one out of four NFPAs with grade 1 uptake, two out of three with grade 1 uptake, and eight out of ten with grade 2 uptake showed tumor shrinkage. Conclusion: In conclusion, there is limited clinical usefulness of dopamine D2 receptor imaging for predicting the clinical efficacy of DA agonist in selected patients with NFPAs. DA agonist therapy in NFPAs can result in tumor stabilization and shrinkage.European Journal of Endocrinology 155 717-723

Treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists

“…These results are in accordance with a previous report in which dopamine D2R imaging using [123] I-epidepride had limited clinical usefulness for predicting the efficacy of DA treatment in NFPA (22). Discordant studies reported the association of dopamine resistance in prolactinomas with low expression levels of the short (34) or long (35) isoforms of D2R.…”

“…Colao and coworkers (18) analyzed 24 studies published between 1981 and 2005, encompassing 199 patients, and report stabilization of over 90% of NFPA masses in patients treated with DA. Five studies (20,21,22,23,24) encompassing 54 patients used cabergoline (mean dose 1-3 mg/week) for the treatment of NFPA (primary treatment or postsurgical remnants) with mean follow-up times between 6 and 12 months. Pooled results indicate that tumor stabilization occurred in 85% of patients (Supplementary Table 4).…”

“…However, dopaminergic binding sites (16) as well as D2R mRNA isoforms (17) are less abundant in NFPA than in prolactinomas, perhaps accounting for the modest rate of tumor shrinkage attained by DAs (18). Small studies, including a report from our own group (19), suggested that DA may retard NFPA growth (20,21,22,23,24), but to date, this potential therapeutic modality has not been broadly practiced.…”

Efficacy of a dopamine-somatostatin chimeric molecule, BIM-23A760, in the control of cell growth from primary cultures of human non-functioning pituitary adenomas: a multi-center study

“…123 I]epidepride D2R imaging showed the absence of correlation between the receptor-binding levels and the long-term efficacy of dopamine agonist treatments in terms of tumor mass stabilization or shrinkage (de Herder et al 2006). Consequently, we cannot provide an answer to the question why approximately one-third of the NFPA studied are insensitive to the chimeric compound.…”

The potential role of D2 dopamine receptors as a target in the management of neuroendocrine tumors

“…Recently, several studies have also shown a possible role for cabergoline in the treatment of non-functional pituitary adenomas. [22][23][24] In this issue of Cancer Biology & Therapy, Grossrubatscher et al show high expression of D 2 dopamine receptors in a large series of neuroendocrine tumors (NETs). 25 This study is the first in the literature to show the expression of D 2 receptors in a wide variety of human NETs, including the stomach.…”