(dtpa-phe(1))-octreotide and Thymoma

The medical approach to patients with secreting or clinically non-functioning pituitary adenoma as made considerable progress thanks to the use of new somatostatin analogs. They were first used to treat acromegaly in the mid 1980s and numerous studies have shown a reduction in GH concentration in over 90% of acromegalic patients. Good results were obtained using slow-release analog treatment also in TSH-secreting adenomas, whereas the therapeutic efficacy of these peptides in clinically non-functioning adenomas is still controversial. Treatment with somatostatin analogs improves symptoms, normalises hormone secretion and in some cases may induce a reduction in the volume of pituitary adenomas. Scintigraphy with octreotide may help to select patients who respond to this form of treatment.

Topics: Acromegaly; Adenoma; Adolescent; Adrenal Gland Neoplasms; Adult; Aged; Antineoplastic Agents, Hormonal; Carcinoma; Humans; Indium Radioisotopes; Insulin-Like Growth Factor I; Kidney Neoplasms; Melanoma; Middle Aged; Octreotide; Pentetic Acid; Peptides, Cyclic; Pheochromocytoma; Pituitary Neoplasms; Predictive Value of Tests; Prolactinoma; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Somatostatin; Thymoma; Thymus Neoplasms; Thyroid Neoplasms; Thyrotropin; Treatment Outcome

Thymic tumours are rare neoplasms which generally follow a slow pattern of growth, showing their aggressiveness locally through the infiltration of adjacent organs and they rarely metastasise hematogenically. In the presence of locally advanced, metastatic or inoperable disease, combined strategies including chemotherapy, radiotherapy and surgery are now being evaluated. Scintigraphy with 111In DTPA-D-Phe 1 octreotide was used for the first time in a relevant series of patients with thymic tumour (13 cases) by our research group. The presence of somatostatin receptors (ss-R) assayed in vivo provided the rationale for the use of a treatment based on the octreotide analog in a patient with thymoma and aplasia of the erythroid series (pure red cell aplasia, PRCA) in whom a complete response for the tumour and the remission of anemia was obtained. The efficacy of this treatment was confirmed by our series of patients with chemoresistant thymic tumour and by national and international confirmations. These data, ranging from in vivo diagnosis to treatment and the in vitro study of receptor expression, confirm that somatostatin plays a major role in thymic tumours.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Humans; Indium Radioisotopes; Neoplasm Proteins; Neoplasm Staging; Octreotide; Pentetic Acid; Prednisone; Protein Isoforms; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Red-Cell Aplasia, Pure; Somatostatin; Thymoma; Thymus Neoplasms; Treatment Outcome

Somatostatin (SS) and SS receptor (SSR) subtypes, code-named sst1-5, are heterogeneously expressed in the normal human thymus. This suggests their involvement in controlling the immune and/or neuroendocrine functions in this organ. Moreover, recently a high in vivo uptake of [111In-DTPA-D-Phe1]octreotide has been reported in patients bearing thymoma. The present study characterizes in vivo and in vitro, functional SS-binding sites in a human thymoma. A high uptake of [111In-DTPA-D-Phe1]octreotide was observed in the chest of a patient with myasthenia gravis due to a cortical thymoma. Specific binding of [125I-Tyr11] SS-14 was found on a membrane preparation of the surgically removed thymoma. Scatchard analysis showed high affinity binding sites (Kd, 47.5 +/- 2.5 pmol/L) with low maximum binding capacity (23.5 +/- 2.5 fmol/mg membrane protein). RT-PCR analysis showed the presence of sst1, sst2A, and a predominant sst3 messenger RNA (mRNA) expression in the tumor tissue. Primary cultured tumor cells expressed sst3 mRNA only. In contrast to the normal thymus, SS mRNA was not expressed. By immunohistochemistry, the tumor cells highly expressed sst3 receptors, weakly expressed sst1 receptors, and showed no immunostaining for sst2A receptors. sst2A immunoreactivity was found in the stromal compartment of the tumor, particularly on the endothelium of small intratumoral blood vessels. In primary cultured tumor cells, both SS and octreotide (10 nmol/L) significantly inhibited [3H]thymidine incorporation by 40.6% and 43.2%, respectively. The following conclusions were reached. 1) As this tumor displayed a high immunoreactivity for sst3 and the cultured tumor cells expressed the sst3 mRNA only, this SSR may be the subtype involved in the inhibition of epithelial tumor cell proliferation by octreotide in vitro. 2) A loss of endogenous SS production in this thymoma might be implicated in the uncontrolled cell growth. 3) In this case, the sst3 may play a role in determining the uptake of [111In-DTPA-D-Phe1]octreotide by in vivo SS receptor scintigraphy.

Topics: Antineoplastic Agents, Hormonal; Cell Division; Female; Gene Expression; Humans; Immunohistochemistry; Indium Radioisotopes; Middle Aged; Octreotide; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Somatostatin; Thymoma; Thymus Neoplasms; Tumor Cells, Cultured

Somatostatin receptor scintigraphy with 111In-[DTPA-D-Phe1]-octreotide has the potential for visualizing primary and recurrent thymomas in patients with myasthenia gravis, whereas thymic hyperplasias fail to accumulate somatostatin analog peptides. We demonstrate somatostatin receptor imaging findings in a patient with a mixed encapsulated thymoma which exhibited intense 111In-[DTPA-D-Phe1]-octreotide uptake in early and late scans. In another patient with a history of malignant thymoma 111In-[DTPA-D-Phe1]-octreotide accumulation was clearly seen in a mass suspected to be a recurrence. This paper describes the imaging protocol including Single Photon Emission Computed Tomography (SPECT) and discusses the clinical applications of this feasible functional imaging method in patients with thymomas.

Topics: Female; Humans; Male; Middle Aged; Myasthenia Gravis; Octreotide; Pentetic Acid; Radiopharmaceuticals; Receptors, Somatostatin; Thymoma; Thymus Neoplasms; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Many tumors with neuroendocrine characteristics express high amounts of somatostatin receptors that enable in vivo imaging with [(111)In-DTPA-D-Phe1]-octreotide. In this study, we have analyzed the feasibility in detecting and characterizing thymic masses by somatostatin receptor scintigraphy (SRS).. Eighteen patients (13 women, 5 men, ages 18-78 yr; mean +/- s.d. = 42.1 +/- 17.6 yr) were enrolled in this study. Eleven patients were studied during diagnosis and seven during routine follow-up. In seven patients, myasthenia gravis was the presenting symptom. SRS was performed within 4 wk after CT and/or MRI. Planar and tomographic images were acquired within 24 hr after the injection of approximately 111 MBq of [(111)In-DTPA-D-Phe1]-octreotide. The scintigraphic results were categorized according to the histologic findings.. Histology diagnosed 10 mixed epithelial/lymphoid thymomas (8 with prevalent epithelial component), 2 thymic carcinomas, 1 thymic carcinoid, 1 lymphangioma and 4 thymic hyperplasias. Two thymoma were Stage I, 3 were Stage II, 2 were Stage III and 5 were Stage IV, as was the thymic carcinoid. Indium-111-DTPA-D-Phe1-octreotide concentrated in primary and/or metastatic sites of thymic tumors, thereby enabling successful external gamma imaging of sites greater than 1.5 cm in size. Tumor-to-lung (T/L) ratios were as high as 7.6-fold (range 1.7-7.6). Untreated thymomas showed higher T/L (4.34 +/- 1.57) than treated ones (2.68 +/- 1.18). No uptake was detectable in the four patients with benign thymic hyperplasia and the patient with the lymphangioma.. Indium-111-DTPA-D-Phe1-octreotide is avidly concentrated within thymic tumors, but it is not concentrated by thymic hyperplasia, which allows differential diagnosis. Thus, in patients with myasthenia gravis, SRS may have a role in characterizing thymic masses, thereby overcoming the limits of cross-sectional imaging modalities.

Topics: Adolescent; Adult; Aged; Carcinoid Tumor; Carcinoma; Diagnosis, Differential; Female; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Octreotide; Pentetic Acid; Radiopharmaceuticals; Thymoma; Thymus Hyperplasia; Thymus Neoplasms; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed