E.P. Krenning

Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS).

Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS).

Somatostatin analogue scintigraphy in granulomatous diseases

Normal as well as activated lymphocytes and macrophages have previously been shown by radioreceptor analysis to express somatostatin receptors (SS-R). The somatostatin (SS) analogue [111In-DTPA-d-Phe1]octreotide (111In-octreotide) is already used successfully in the visualization of a variety of neuro-endocrine tumours and malignant lymphomas. In the present study 20 consecutive patients were investigated, 12 with sarcoidosis, one with both sarcoidosis and aspergillosis, four with tuberculosis and three with Wegeners granulomatosis. For in vivo SS-R imaging, total-body scintigraphy was performed 24 and 48 h after the administration of 111In-octreotide. Granuloma localizations could be visualized in all patients studied; additional sites were found in nine patients with sarcoidosis and in two patients with tuberculosis. In vitro autoradiography of fresh tissue biopsies, using the SS analogue [125I-Tyr3]octreotide, showed binding at sites that were microscopically identified as granulomatous inflammation. These observations demonstrate the expression of SS-R by human granulomas. This scintigraphy procedure may contribute to a more precise staging and evaluation of granulomatous diseases, but more importantly it may be a sensitive indicator of the efficacy of glucocorticoid and/or immunosuppressive therapy.

Somatostatin and the immune and haematopoetic system; a review

SS-R and SS have been demonstrated in non-pathological and pathological lymphoid tissue and may play a regulatory, mostly inhibitory, role in the immune response. SS is produced by lymphocytes and monocytes which suggests an autocrine or paracrine regulatory role, but SS may be released as well by nerve endings. It can therefore be hypothesized that apart from a role of SS in local, immunomodulation of cells belonging to the immune system, a second pathway exists in which this peptide exerts its effects via neuroendocrine modulation of the immune response which might represent a direct regulatory relation between the nervous and the immune system. The presence of SS-R in lymphoid neoplasm cells and in diseases involving activated mononuclear leukocytes allows the visualization of these diseases using octreotide scintigraphy. This technique may be used in the evaluation of the spread of these diseases and to monitor their response to therapy. Moreover, the presence of SS-R in immune diseases warrants studies on the efficacy of treatment with octreotide of patients suffering from these diseases.

111In-octreotide scintigraphy in oncology

Various tumors of neuroendocrine origin that have amine precursor uptake and decarboxylation (APUD) characteristics can be visualized in vivo after intravenous (IV) injection of the somatostatin analogue, [123I-Tyr3]-octreotide. However, the relatively short effective half-life of this compound and the high background of radioactivity in the abdomen are drawbacks to its application. Therefore, an 111In-coupled somatostatin analogue ([111In-DTPA-D-Phe1]- octreotide) was developed. This analogue is excreted mainly via the kidneys, with 90% of the dose being present in the urine 24 hours after injection. Using 111In-octreotide scintigraphy, seven of seven gastrinomas, four of seven insulinomas, one of one glucagonomas, three of three unclassified APUDomas, and none of 18 exocrine pancreatic carcinomas were visualized. Also, 19 of 19 carcinoids, 15 of 15 glomus tumors, eight of 12 medullary thyroid carcinomas, six of six small-cell lung carcinomas, four of four growth hormone-producing and six of nine clinically nonfunctioning pituitary adenomas were visualized. Apart from APUD cell-derived tumors, 111In-octreotide scintigraphy was also successfully applied in visualizing breast cancer, lymphomas, and granulomas. In 39 of 50 patients with breast carcinoma, 10 of 11 patients with non-Hodgkins lymphomas, three of three patients with Hodgkins disease, and eight of eight patients with sarcoidosis, tumor sites accumulated radioactivity during octreotide scintigraphy. In a considerable number of patients with carcinoids and glomus tumors, and also in patients with granulomas and lymphomas, 111In-octreotide scintigraphy showed more tumor sites than did conventional imaging techniques. The results of imaging in vivo correlated with the somatostatin-receptor status on the tumors in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Somatostatin Receptor Scintigraphy in Carcinoids, Gastrinomas and Cushing’s Syndrome

High numbers of high-affinity somatostatin binding sites have been found on carcinoid tumors, gastrinomas, small cell lung cancers and the majority of medullary thyroid cancers, enabling in vivo visualization of these tumors with octreotide scintigraphy. A comparison of the results obtained at our institution and another 15 centers in Europe show a few remarkable similarities and differences. The overall sensitivity of octreotide receptor scintigraphy to detect the primary GEP tumor and its metastases is high, e.g. 80-90%. The main difference was found in gastrinomas and to a lesser extent in insulinomas. These differences might be attributed to different scanning protocols. Furthermore, octreotide scintigraphy also has a high sensitivity to localize the primary tumor and its metastases causing Cushings syndrome by ectopic production of ACTH or CRH. Octreotide scintigraphy is a new, sensitive and noninvasive technique to localize somatostatin receptor expressing endocrine tumors and their metastases.

Intraoperative nuclear guidance in benign hyperparathyroidism and parathyroid cancer.

The success of parathyroid surgery is determined by the identification and removal of all hyperactive parathyroid tissue. Ectopic location of parathyroid tumours and fibrosis due to previous operations can cause failure of parathyroidectomy. Parathyroid tumours accumulate and retain 2-methoxyisobutylisonitrile (MIBI) labelled with technetium-99m. This study assesses the value of intra-operative localization of parathyroid tumours using a hand-held gamma detector in patients with hyperparathyroidism and parathyroid cancer. Twenty patients undergoing their first operations for hyperparathyroidism, 15 patients undergoing reoperations for either persistent or recurrent hyperparathyroidism and two patients with parathyroid cancer were studied. Radioactivity in the neck and the mediastinum was recorded by a gamma detector after administration of 370 MBq99mTc-MIBI. Surgical findings and postoperative serum levels of calcium were documented. The sensitivity of the gamma detector in identifying parathyroid tumours was 90.5% in first parathyroidectomies, 88.9% in reoperations for either persistent or recurrent hyperparathyroidism and 100% in parathyroid cancer. One false-positive result was due to a thyroid nodule. Hypercalcaemia ceased in all but one patient postoperatively. It is concluded that employment of the gamma detector is to be advocated in first parathyroidectomies when a parathyroid tumour cannot be discovered, in reoperations for either persistent or recurrent hyperparathyroidism and in surgery for parathyroid cancer.

Somatostatin Receptor Scintigraphy in Non-Medullary Thyroid Cancer

8 patients with papillary cancer (4 with metastases, 4 in remission), 7 follicular cancer patients (6 with metastases), 2 patients with anaplastic thyroid cancer and 4 other non-medullary thyroid cancer patients all received an intravenous bolus injection of 220 MBq [111In-DTPA-D-Phe1]octreotide. Planar anterior and posterior gamma camera images of head-neck, chest and abdomen were obtained 24 and 48 h after injection. All primary cancers showed [111In-DTPA-D-Phe1] octreotide uptake; none occurred in patients in remission. The results were compared with conventional radio-iodine scintigraphy in patients with metastasised, differentiated thyroid cancer.

Somatostatin receptor scintigraphy in the follow-up of patients with differentiated thyroid cancer

The aim of this study was to compare the results of somatostatin receptor scintigraphy (SRS) and of radioiodine scintigraphy in patients with metastatic differentiated thyroid carcinoma during L-thyroxine suppression therapy and after withdrawal. Twenty-five patients were studied: 16 patients had papillary cancer and 12 of them had metastatic disease; 9 patients had follicular cancer and 7 of these had known metastases. In 7 patients SRS was performed during thyroxine withdrawal, in 12 during thyroxine therapy within 9 months from radioiodine scintigraphy, in 6 others both during suppression therapy and after withdrawal. SRS was positive in 18 of 25 (72%) patients. It demonstrated lesions in 11 of 13 (85%) patients after thyroxine withdrawal and in 12 of 18 (67%) patients during thyroxine suppression. In 6 patients in whom a direct comparison was made before and after withdrawal, essentially the same information was obtained. Six of 8 (75%) patients with lesions that did not concentrate radioiodine showed uptake of labeled octreotide in these lesions. In 5 of 17 (29%) patients whose tumors concentrated radioiodine, no uptake was found during SRS. Conclusions: 1) in patients with metastatic differentiated thyroid carcinoma, tumor sites can be visualized using SRS; 2) there is no need to withdraw patients from suppression therapy in order to perform SRS; 3) in some patients whose lesions do concentrate labeled octreotide but not radioiodine, the use of somatostatin analogues labeled with 111In or [90Y] can provide new therapeutic options.

Comparison of iodine-123 epidepride and iodine-123 IBZM for dopamine D2 receptor imaging in clinically non-functioning pituitary macroadenomas and macroprolactinomas

Abstract. We compared pituitary iodine-123 epide- pride single-photon emission tomography (SPET) and 123I-IBZM SPET for the in vivo imaging of dopamine D2 receptors in 15 patients with clinically non-functioning pituitary adenomas. Four patients with dopamine agonist-sensitive macroprolactinomas were studied as positive controls. The uptake of radioactivity in the pituitary was established using a visual scoring system and an uptake index calculated by dividing the average count rates in the pituitary area by the average count rates in the cerebellum. All four macroprolactinomas showed specific binding of 123I-epidepride, but only one showed specific binding of 123I-IBZM. Specific binding of 123I-epidepride was demonstrated in 9 of the 15 clinically non-functioning pituitary adenomas (60%), but specific binding of 123I-IBZM was shown in only 6 of these 15 cases (40%). The uptake of 123I-epidepride in the pituitary region was consistently higher than that of 123I-IBZM. None of the patients who showed absence of uptake of 123I-epidepride in the pituitary area showed uptake of 123I-IBZM in this area. In conclusion: 123I-epidepride SPET is superior to 123I-IBZM SPET for the visualization of dopamine receptor-positive pituitary adenomas. Therefore, 123I-epidepride should replace 123I-IBZM for future D2 receptor SPET studies of pituitary adenomas. 123I-epidepride SPET potentially might serve to predict the response of clinically non-functioning pituitary adenomas to dopamine agonist therapy.

In vivo imaging of pituitary tumours using a radiolabelled dopamine D2 receptor radioligand

OBJECTIVE Knowledge of the dopamine D2 receptor status of pituitary tumours may play a predictive role in differential diagnosis and therapeutic decisions. This study was performed to evaluate the value of pituitary dopamine D2 receptor scintigraphy with (S)‐2‐hydroxy‐3‐123I‐iodo‐6‐methoxy‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]benzamide (123I‐IBZM) in the diagnostic evaluation of patients with pituitary tumours.