title: Correlation of scintigraphic results using 123I-methoxybenzamide with hormone levels and tumor size response to quinagolide in patients with pituitary adenomas.
abstract: The efficacy of dopaminergic agents in the medical treatment of pituitary adenomas is well known. Quinagolide is a nonergot derivative dopamine agonist, which binds dopamine D2 receptors with high affinity. The treatment with this drug is reported to suppress hormone levels and to cause tumor shrinkage in prolactinomas and in a few GH-secreting pituitary adenomas. In clinically nonfunctioning pituitary adenomas (NFPA), the efficacy of quinagolide treatment is controversial. The scintigraphy of the pituitary region using 123I-methoxybenzamide (123I-IBZM) allows us to visualize in vivo the expression of dopamine D2 receptors on pituitary tumors. In this study, the pituitary scintigraphy with 123I-IBZM was performed in 14 patients with macroadenoma before starting a long-term treatment with quinagolide: 6 NFPA with high circulating alpha-subunit levels, 4 PRL-secreting, and 4 GH-secreting adenomas. A 3-point score was used to grade the ligand accumulation within the pituitary adenomas: 0 = negative, 1 = moderate uptake (equal to that recorded in the cerebral cortex), and 2 = intense uptake (equal to that recorded in the basal nuclei). The treatment with quinagolide was carried out at the dose of 0.3-0.6 mg/day for 6-12 months. Clinical, biochemical and hormonal assessment was repeated monthly during the first 3 months, then quarterly. Sellar magnetic resonance imaging was performed before and after 6 and 12 months of quinagolide treatment, to evaluate tumor shrinkage (> 25% of baseline size). In all 14 patients, a significant positive correlation was found between the degree of 123I-IBZM uptake and the clinical response to quinagolide treatment (r = 0.90; P < 0.001). In particular, the normalization of serum alpha-subunit and PRL levels, respectively, was achieved in 3 patients with NFPA and in 2 patients with prolactinoma, who showed intense 123I-IBZM uptake in the pituitary region. In 4 of these 5 patients with positive scan, a significant tumor shrinkage occurred between 6 and 12 months after the beginning of quinagolide treatment. In all patients with GH-secreting adenoma, no significant uptake of 123I-IBZM was found and no significant decrease of circulating GH and/or insulin-like growth factor-I levels, and tumor shrinkage was obtained during long-term treatment with quinagolide. In conclusion, the pituitary scintigraphy with 123I-IBZM can be considered a useful tool to indicate adenomas with significant expression of functioning D2 receptors. This innovative technique may predict the response to long-term treatment with quinagolide in patients with NFPA, where the lack of pituitary hormone hypersecretion makes difficult the monitoring of medical treatment efficacy.
authors.affiliation: Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Ferone
authors.forename: S
authors.initials: S
authors.lastname: Lastoria
authors.forename: A
authors.initials: A
authors.lastname: Colao
authors.forename: P
authors.initials: P
authors.lastname: Varrella
authors.forename: G
authors.initials: G
authors.lastname: Cerbone
authors.forename: W
authors.initials: W
authors.lastname: Acampa
authors.forename: B
authors.initials: B
authors.lastname: Merola
authors.forename: M
authors.initials: M
authors.lastname: Salvatore
authors.forename: G
authors.initials: G
authors.lastname: Lombardi
mesh_terms: D000236:Adenoma / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D000634:Aminoquinolines / Q000627:therapeutic use*; D001549:Benzamides; D015415:Biomarkers / Q000097:blood; D018491:Dopamine Agonists / Q000627:therapeutic use*; D015292:Glycoprotein Hormones, alpha Subunit / Q000097:blood; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007457:Iodine Radioisotopes; D008279:Magnetic Resonance Imaging; D010911:Pituitary Neoplasms / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D011759:Pyrrolidines; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000634:Aminoquinolines; D001549:Benzamides; D015415:Biomarkers; D018491:Dopamine Agonists; D015292:Glycoprotein Hormones, alpha Subunit; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C046650:quinagolide; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D011388:Prolactin