Results of somatostatin receptor scintigraphy do not predict pituitary tumor volume- and hormone-response to octreotide therapy and do not correlate with tumor histology

Abstract

The value of somatostatin receptor scintigraphy (SRS) to predict the effect of somatostatin analog therapy on pituitary adenomas is not clear, due to the use of different radiopharmaceuticals (123I-Tyr3-octreotide and 111In-pentetreotide) and the small number of patients in previous studies. We used 111In-pentetreotide scintigraphy in 49 patients in order to (i) correlate SRS results with basal tumor volume as well as volume- and hormone-response to 3 months of octreotide therapy (Oct-Tx). (ii) identify tumor remnants after incomplete surgery and (iii) evaluate any correlation with immuno histology. Twenty-five patients had a GH-secreting adenoma (GH-A, 15 prior to intended surgery, 10 with persistent/recurrent disease after previous therapy). Twenty-four patients had a clinically non-functioning adenoma (NF-A). For SRS, planar and single photon emission computer tomographic images (SPECT) were recorded 4 h and 24 h post injection. SRS grading was as follows: GO, no uptake: G1, uptake comparable to normal pituitary; G2, increased uptake: G3, very intense uptake. G2/3 was seen in 8/25 GH-A and in 12/24 NF-A. Pretreatment tumor volume (magnetic resonance imaging (MRI) tended to be related to 111In-pentetreotide uptake in GH-A with a tumor visible on MRI (G0/1 (n = 10) vs G2/3 (n = 8): 3.6 +/- 1.9 vs 10.5 +/- 6.5 cm3 (mean +/- S.E.), P = 0.051), but not in NF-A (G0/1 (n = 12) vs G2/3 (n = 12): 17.0 +/- 10.1 vs 14.3 +/- 3.6 cm3). SRS did not identify a tumor remnant in the 7 MRI-negative patients with persistent post-operative acromegaly. Basal GH (6-h profile) and IGF-1 in GH-A did not correlate with SRS results (G0/1 (n = 17) vs G2/3 (n = 8), GH: 32.3 +/- 18.2 vs 29.3 +/- 7.4 micrograms/l IGF-I: 851 +/- 80 vs 1038 +/- 153 micrograms/l). During Oct-Tx of GH-A neither tumor shrinkage nor GH suppression was related to SRS results. In 6 NF-A classified as gonadotropinomas (by their plasma glycoprotein hormone or alpha-subunit concentrations, basally and/or in response to TRH) 111In-pentetreotide uptake was not different from that of the non-gonadotropin/non-secreting adenomas. SRS results were not related to the immunohistological subtype in 22 GH-A (monohormonal mixed somatotrope/lactotrope, plurihormonal) or in 22 NF-A (null-cell adenomas, gonadotropinomas silent hormonal adenomas). We conclude that 111In-pentetreotide SRS reflects tumor volume poorly in GH-A and not at all in NF-A. It does not predict the effect of Oct-Tx on the volume of both GH-A and NF-A, nor on the GH concentration in GH-A. 111In-pentetreotide SRS is unable to identify post-operative tumor remnants not visible on MRI.

A luteinizing hormone-, alpha-subunit- and prolactin-secreting pituitary adenoma responsive to somatostatin analogs: in vivo and in vitro studies

“…Among 48 patients with non-functioning adenomas and gonadotrophinomas (25,26), a significant (.20%) tumour shrinkage was documented in only 7 cases (15%). The SSTR scintigraphy using In111-pentreotide was of poor predictive value in one study (25). A possible explanation of this latter finding is that In111-pentreotide presents with binding affinities towards the SSTR subtypes different from those of octreotide.…”

DG3173 (somatoprim), a unique somatostatin receptor subtypes 2-, 4- and 5-selective analogue, effectively reduces GH secretion in human GH-secreting pituitary adenomas even in Octreotide non-responsive tumours

“…In addition, heterodimerisation of the different ssts upon binding would preclude any clear-cut correlation between receptor expression and signal transduction after ligand binding in multiligand SSA (9,10). We have previously demonstrated a lack of correlation between the results of sst scintigraphy (reflecting sst2-status of the adenoma) and the effect of Octreotide on GH secretion or tumour shrinking in acromegaly (59).…”

Clinical implications of somatostatin-receptor scintigraphy in ophthalmic Graves' disease

“…In fact, SRS is used to detect disease sites in neuroendocrine and non-neuroendocrine malignancies (12) and to reveal the presence of activated lymphocytes in inflammatory foci of several autoimmune diseases such as rheumatoid arthritis and Sjo Ègren's disease (13). SRS has been proposed to select candidates responsive to specific peptide treatment (14±16), though in patients with pituitary adenomas this latter evidence is under debate (17,18). A potentially relevant role for SRS in the pretreatment evaluation of TAO has been suggested recently (19) (21) reported that the uptake of 111 In-DTPA-d-Phe 1 -octreotide (measured quantitatively as counts/voxel orbit:brain ratio on filtered, transverse/oblique orbital SPECT reconstruction 4 and 24 h after the injection of 110 MBq radiotracer) was significantly higher in 34 patients with clinically active TAO than in 6 patients with inactive disease and in 10 controls.…”