Orbital Scintigraphy with [¹¹¹In-Diethylenetriamine Pentaacetic Acid-D-Phe¹]-Octreotide Predicts the Clinical Response to Corticosteroid Therapy in Patients with Graves’ Ophthalmopathy

Abstract

Corticosteroid treatment is successfully used in Graves' ophthalmopathy, and its effect varies according to the phase of the disease. The infiltration of the orbit by activated lymphocytes may explain the effectiveness of corticosteroid therapy. Scintigraphy with [111In-DTPA-D-Phe1]-octreotide was recently used to reveal the presence of activated lymphocytes in foci of autoimmune diseases, because elevated amounts of somatostatin receptors are expressed in the surface of these cells. The aim of the current study was to evaluate whether the degree of orbital [111In-DTPA-D-Phe1]-octreotide uptake is able to predict the response to corticosteroid therapy in patients with Graves' ophthalmopathy. Ten patients with Graves' ophthalmopathy entered the study. In all patients scintigraphy was performed, and subsequently, corticosteroid therapy (methylprednisolone, 1 g i.v. for 2 consecutive days a week for 6 weeks) was given. Clinical activity of Graves' ophthalmopathy was evaluated before and after treatment by calculating the ophthalmopathy index (OI). Planar and single photon emission computed tomography (SPECT) images of the head were obtained 24 h after the i.v. injection of 120-190 MBq of [111In-DTPA-D-Phe1]-octreotide. Radioligand uptake within each orbit (O) and brain (B) was measured using the region of interests (ROI) method and the O-to-B ratio was determined. According to the O-to-B ratio, the images were classified using the following three points score: 0 = O-to-B ratio < or =1; 1 = O-to-B ratio between 1 and 2.5; 2 = O-to-B ratio > or =2.5. The value of OI, measured before and after corticosteroid treatment, was correlated to the scintigraphic score. A significant change of OI was observed between posttreatment and pretreatment evaluation both in orbits with score 2 (OI: 15.4 +/- 1.5 vs. 9.6 +/- 0.5, P < 0.005) and in those with score 1 or 0 (OI: 12.9 +/- 1.5 vs. 11.5 +/- 1.4, P < 0.05) at the scintigraphy. However, when the OI was calculated excluding the changes in the soft tissue, which generally occur in all patients independently from the phase of the disease, a significant change of OI was observed only in the orbits with score 2 (OI: 12.9 +/- 1.3 vs. 8.3 +/- 0.5, P < 0.01) but not in those with score 0 or 1 (OI: 11.2 +/- 1.3 vs. 10.4 +/- 1.3). In particular, 6 weeks after corticosteroid treatment, the patients with orbital score 2 at the scintigraphy had a significant improvement of soft tissue changes, proptosis, lagophthalmos, extraocular muscle movements impairment, and diplopia, whereas patients with score 0 or 1 had only a significant improvement of the soft tissue inflammation. In conclusion, the current preliminary data suggested that [111In-DTPA-D-Phe1]-octreotide scintigraphy is able to predict the clinical response to corticosteroid treatment in patients with Graves' ophthalmopathy, and may be considered an useful approach to select the patients for the proper treatment.

Somatostatin receptor gene expression and inhibitory effects of octreotide on primary cultures of orbital fibroblasts from Graves' ophthalmopathy

“…We also show that retroorbital fibroblasts specifically bind SST-14, and respond in vitro to the SST analogue octreotide by inhibition of cAMP production and cell growth. The presence of functional ssts on retroorbital tissues of patients with GO was suggested by the uptake of 111 In-DTPA--Phe 1 -octreotide into the orbits during the  2. sst subtype mRNA expression in primary fibroblast cultures from retroorbital tissues GO1 GO2 GO3 GO4 GO5 GO6 GO7 GO8 GO9 GO10 C1 C2 C3 C4 C5 active phase of the disease (Chang et al 1991, Postena & Krenning 1994, Kahaly et al 1995, Krassas et al 1995, Colao et al 1998 (Reisine & Bell 1995, Patel 1997. Octreotide, at physiological concentrations, inhibited cAMP accumulation in vitro, demonstrating that, as in other cell systems (Patel 1997), ssts in retroorbital fibroblasts are negatively coupled to adenyl-cyclase activity.…”

“…Accumulation of radiolabelled SST analogue in retroorbital tissue has been demonstrated in vivo by 111 In-DTPA--Phe 1 -octreotide (Octreoscan) scintigraphy (Chang et al 1991, Postena & Krenning 1994, Kahaly et al 1995, Krassas et al 1995, Colao et al 1998, suggesting the presence of specific binding sites for octreotide on the orbit components. It is not clear whether octreotide binds to retroorbital fibroblasts or to infiltrating immune cells.…”

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

“…The results of orbital 111 In-DTPA-d-Phe 1 -octreotide uptake predicted the response to corticosteroid therapy in these patients (28). In 10 patients with TAO undergoing SRS before corticosteroid therapy (methylprednisolone, 1 g i.v.…”

“…3). In particular, 6 weeks after corticosteroid treatment, 7 patients with orbital scores of 2 in the scintigraphy had significant improvements in soft-tissue inflammation, proptosis, lagophthalmos, extraocular muscle-movement impairment and diplopia after treatment, whereas patients with scores of 0 or 1 had significant changes only in symptoms with soft-tissue involvement (28). Lending further support to our previous observation, Nocaudie et al (30), in a prospective study on 17 patients presenting with severe ophthalmopathy, used hormonal and immunological investigations, orbital radiological imaging (CT scans or MRI), visual functional examinations and orbital SRS before the start of steroid and/or radiotherapy treatment.…”

Novel Approaches to the Management of Graves` Ophthalmopathy

“…Octreoscan positivity correlates with other indicators of activity of the ophthalmopathy, such as high CAS 10 or T2-relaxation time of the extraocular muscles at magnetic resonance imaging 14 . Thus, a positive octreoscan is an indicator of GO activity 15 and may predict a subsequent favorable response not only to SMSa therapy but also to high-dose glucocorticoids and/or orbital radiotherapy 11,[16][17][18] . Limitations to a wide-scale use of octreoscan in making a therapeutic decision for GO patients include: high demand of this technique in terms of accuracy needed for prediction, high cost, a not negligible radiation burden and relative lack of specificity (i.e., the number of false positives in other inflammatory or noninflammatory orbital disorders) 15 .…”