Somatostatin receptor imaging in intracranial tumours

The somatostatin analogue [111In-DTPA-d-Phe1]-octreotide (111In-octreotide) allows scintigraphic visualization of somatostatin receptor-expressing tissue. While it is well known that a large variety of tissues express somatostatin receptors and 111In-octreotide scintigraphy has a clearly defined role in various neuroendocrine diseases, the clinical value of 111In-octreotide scintigraphy in brain tumours is still under clinical investigation. In 124 patients with 141 brain lesions (63 meningiomas, 24 pituitary adenomas, 10 gliomas WHO class I and II, 12 gliomas WHO class III and IV, 11 neurinomas and 2 neurofibromas, 7 metastases and 12 other varieties: three non-Hodgkin B-cell lymphomas, two epidermoids, one abscess, one angioleiomyoma, one chordoma, one haemangiopericytoma, one osteosarcoma, one plasmacytoma and one pseudocyst), 111In-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 110-220 MBq 111In-octreotide. Planar images of the head in four views with a 128x128 matrix and single-photon emission tomographic images (64x64 matrix) were acquired, and lesions were graded according to qualitative tracer uptake. Fifty-nine of the 63 meningiomas showed moderate to intense tracer uptake. Nine of 24 pituitary adenomas were visible; the remaining 15 did not show any tracer uptake. None of the class I and II gliomas with an intact blood-brain barrier were detected whereas 11/12 class III and IV gliomas showed 111In-octreotide uptake. None of the neurinomas or neurofibromas were positive. Five of seven metastases were classified as positive, as were the osteosarcoma, two of three non-Hodgkin B-cell lymphomas, one abscess, one angioleiomyoma, one chordoma and one haemangiopericytoma. The other varieties (one non-Hodgkin B-cell lymphoma, two epidermoids, one plasmacytoma and one pseudocyst) did not show 111In-octreotide uptake. The results demonstrate that a large variety of intracranial lesions express somatostatin receptors and therefore can be visualized by [111In-DTPA-d-Phe1]-octreotide scintigraphy. This technique can be valuable in the differentiation between meningiomas and pituitary adenomas, based on qualitative tracer uptake. [111In-DTPA-d-Phe1]-octreotide scintigraphy allows differentiation between meningiomas and neurinomas or neurofibromas and therefore provides complementary information to computed tomography or magnetic resonance imaging. Furthermore, this technique allows differentiation between scar tissue and recurrent meningiomas postoperatively and can help in non-invasive tumour differentiation of multiple intracranial lesions, which can be of value in defining the most adequate therapeutic strategy.     

Effects of arginine, growth hormone-releasing hormone (GHRH) and neostigmine administered singly or in paired combinations on growth hormone (GH) release in pigs

OBJECTIVE: A multicentre study was undertaken to determine the value of somatostatin receptor (sst) scintigraphy in predicting hormonal and visual responses to octreotide treatment in GH-secreting and non-functioning pituitary adenomas. SUBJECTS AND METHODS: Somatostatin receptor scintigraphy was performed in 48 patients (19 acromegaly, 29 non-functioning pituitary adenomas with ophthalmological defects). Results were expressed as an uptake index of the pituitary area. A threshold for positivity was determined in 23 subjects considered as controls. Thirty-five patients were treated for 1 month with octreotide (300 micrograms daily). The therapeutic response was assessed on GH and IGF-I suppression or evolution of the ophthalmological defects. The relationships between the somatostatin receptor scintigraphy result, the therapeutic effect of octreotide and in vitro studies performed in 12 tumours were studied. RESULTS: From the results of control subjects the uptake index threshold for positivity was 2. In patients, somatostatin receptor scintigraphy was positive in 64% and there was no relationship between uptake index and tumour size. In GH tumours, somatostatin receptor scintigraphy was positive in 68%; uptake index was related to octreotide-induced GH and IGF I suppression. The positive predictive value was 100% and the negative predictive value was 50%. In vitro studies showed detectable binding sites for somatostatin with sst2 and sst5 expression in the 4 GH tumours studied although somatostatin receptor scintigraphy was negative in 2 cases. In non-functioning pituitary adenomas somatostatin receptor scintigraphy was positive in 62%. Based on visual effects, the positive predictive value was 61% and the negative predictive value was 100%. A wide distribution of somatostatin binding sites was found in 8 non-functioning pituitary adenomas with expression of sst2 only. CONCLUSION: In the conditions of the study, in patients with acromegaly, positive somatostatin receptor scintigraphy predicts a hormonal response but the value of somatostatin receptor scintigraphy is limited by its low negative predictive value. In patients with non-functioning pituitary adenomas, negative somatostatin receptor scintigraphy predicts that there will be no visual improvement during octreotide treatment.     

111In-pentetreotide scintigraphy is superior to 123I-MIBG scintigraphy in the diagnosis and location of chemodectoma

Chemodectomas, or glomus tumours, are unusual head and neck paragangliomas. A non-invasive imaging technique, 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy, has long been used for the diagnosis of all types of paraganglioma. The aim of this study was to evaluate and compare classic 123I-MIBG scintigraphy with the more recent 111In-pentetreotide scintigraphy in the diagnosis and location of chemodectomas. We performed 123I-MIBG and 111In-pentetreotide scintigraphy in eight patients (7 females, 1 male) with histologically or radiologically confirmed chemodectomas (five carotid body and three jugulotympanic chemodectomas). 123I-MIBG uptake was visualized in four patients on planar views and SPET images (sensitivity 50%); uptake was low in three patients. Using 111In-pentetreotide scintigraphy, all chemodectomas in eight patients were visualized (sensitivity 100%) and 111In-pentetreotide uptake was high in all cases. In conclusion, our results indicate that 111In-pentetreotide scintigraphy is superior to 123I-MIBG scintigraphy in the diagnosis and location of chemodectomas. In-pentetreotide or 123I-MIBG uptake suggests a neuroendocrine origin, providing important functional information in the diagnosis of chemodectomas. Moreover, 111In-pentetreotide scintigraphy permits a good classification of patients with or without somatostatin receptors in the chemodectoma in the application of pharmacological therapy with somatostatin analogues to inoperable tumours. The main therapeutic action of cold somatostatin analogues is to inhibit hormonal hypersecretion in different neuroendocrine tumours. In chemodectomas, however, the most important effect of somatostatin analogues is to reduce tumour volume or inhibit growth progression.     

Somatostatin receptor scintigraphy of carcinoid tumours using the [111In-DTPA-D-Phe1]-octreotide

Somatostatin-receptor scintigraphy using the 111In-labelled somatostatin-analogue octreotide ([111In-DTPA-D-Phe1]-octreotide) was performed in 40 patients with carcinoid tumours. In 31/40 patients, this scintigraphy proved positive compared with the 33/40 patients whose tumours were disclosed on CT scans. In addition, 18 previously unidentified lesions were detected with this scintigraphy. Two of these lesions represented previously undetectable primary tumours. It is concluded that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]-octreotide has a future role in the staging of patients with carcinoid disease.     

Somatostatin in neuroblastoma and ganglioneuroma

Neuroblastoma, a childhood tumour of the sympathetic nervous system, may in some cases differentiate to a benign ganglioneuroma or regress due to apoptosis. Somatostatin may inhibit neuroblastoma growth and induce apoptosis in vitro and was therefore investigated. Using a radioimmunoassay, we found that all ganglioneuromas contained high somatostatin concentrations (> 16 pmol/g), significantly higher than neuroblastomas (n = 117, median 2.8 pmol/g), healthy adrenals, Wilms' tumours, phaeochromocytomas and other neuroendocrine tumours (P < 0.001). Neuroblastomas contained more somatostatin than control tumours (P < 0.001-0.05). Neuroblastomas amplified for the MYCN oncogene contained less somatostatin than non-amplified tumours (1.2 pmol/g versus 4.0 pmol/g, respectively; P = 0.026). In a clinically unfavourable neuroblastoma subset (age > 12 months, stage 3 or 4) 16 children with high concentrations of somatostatin in primary tumours had a better prognosis than 23 with low somatostatin (46.7% versus 0% survival at 5 years, P < 0.005). Scintigraphy using 111In-pentetreotide identified tumours expressing high-affinity somatostatin receptors in vivo. However, no significant correlation was found between somatostatin receptor expression and peptide content in 15 tumours. Similarly, human SH-SY5Y neuroblastoma xenografts grown in nude rats showed low somatostatin concentrations, but were positive for somatostatin receptor scintigraphy. Treatment of these rats with the somatostatin analogue octreotide seemed to upregulate in vivo receptor expression of somatostatin and vasoactive intestinal peptide more effectively than 13-cis retinoic acid. In conclusion, somatostatin in neuroblastoma is associated with differentiation to benign ganglioneuromas in vivo and favourable outcome in advanced tumours. Furthermore, somatostatin receptor scintigraphy may identify tumours with high-affinity receptors in children that might benefit from targeted therapy using synthetic somatostatin analogues.     

Use of somatostatin analogue scintigraphy in the localization of recurrent medullary thyroid carcinoma

Detection of recurrence of medullary thyroid carcinoma (MTC) remains a diagnostic problem. Increased serum tumour marker levels frequently indicate recurrence while conventional imaging techniques (CIT) are non-diagnostic. In this study, we performed indium-111 octreotide scintigraphy and CIT in a series of 20 patients with MTC presenting with elevated serum tumour markers after surgery. 111In-octreotide whole-body studies detected 15 pathological uptake foci in 11 of the 20 patients studied and CIT detected 17 lesions in 11 of the 20 patients. Ten patients underwent reoperation, five of them with positive 111In-octreotide scintigraphy and CIT and two with positive isotopic exploration and negative CIT. Surgical findings demonstrated that the results of isotopic study and CIT had been false-positive for MTC in one case (sarcoidosis). The six patients with true-positive 111In-octreotide studies had significantly higher basal calcitonin (CT) and carcinoembryonic antigen (CEA) levels than the patients with negative isotopic studies. The expression of somatostatin receptor (SSTR) subtypes by PC-PCR could be investigated in four cases with a positive isotopic study. Among the three cases with a true-positive study, SSTR2, the SSTR subtype that preferentially binds to the somatostatin analogue octreotide, was detected in two, SSTR5 was demonstrated in the three, and SSTR3 was detected in one. No subtype of SSTR was detected in the case with a final diagnosis of sarcoidosis. We conclude that 111In-octreotide has limited sensitivity in detecting recurrence in patients with MTC, although its sensitivity may improve with high serum CT levels. This radionuclide imaging technique should be employed when conventional imaging techniques are negative or inconclusive or when the presence of somatostatin receptors may provide the basis for treatment with somatostatin analogues.     

Effects of ligand priming and multiple-dose injection on tissue uptake of 111In-pentetreotide in rats

In patients undergoing somatostatin receptor scintigraphy, treatment with octreotide (Sandostatin) is usually discontinued 24-48 h before and after injection with the radioligand 111In-pentetreotide ([111In-DTPA(O)]octreotide) (Octreoscan) because octreotide competes with radioligand for the same receptors. However, D?rr et al. and Soresi et al. reported improved visualization of carcinoid and small cell lung cancer lesions, respectively, during continued octreotide treatment. We found that intravenous administration of unlabeled octreotide to rats inhibited the binding of an optimal dose (0.5 microg) of 111In-pentetreotide to somatostatin receptors in pancreas and adrenals in a mass- and time-dependent way. Pretreatment with unlabeled octreotide never increased receptor binding of 111In-pentetreotide. Administration of 100 microg of octreotide decreased receptor-bound radioactivity if given simultaneously with or 10 or 20 min after injection of the radioligand, but had no effect if given 30 min after the radioligand. These findings indicate rapid processing of receptor-bound octreotide and suggest that octreotide treatment of patients undergoing 111In-pentetreotide scintigraphy may be reinitiated as soon as 1 h after radioligand administration.     

Indium-111 pentetreotide single-photon emission tomography in patients with TSH-secreting pituitary adenomas: correlation with the effect of a single administration of octreotide on serum TSH levels

Few data are available on the visualization of somatostatin receptors in vivo in patients with thyrotropin (TSH)-secreting adenoma. We studied five patients with TSH-secreting adenomas using single-photon emission tomography (SPET) after administration of indium-111 pentetreotide. The intensity of 111In-pentetreotide uptake by the tumours was correlated with the degree of TSH suppression after a single administration of 100 microg octreotide s. c. Five patients (three women and two men) aged 27-46 years were investigated. Except for one patient with acromegaly, all had pure TSH-secreting tumours. One patient was previously untreated, while two had received octreotide, one antithyroid drugs, and one radioiodine. In all patients SPET demonstrated increased uptake of 111In-pentetreotide by the pituitary adenoma. The target to non-target ratio (T/nT) of 111In-pentetreotide uptake was higher than 10 in three patients. Administration of 100 microg octreotide s. c. caused a significant reduction in TSH levels from 4.8+/-1.4 mU/l to a nadir of 3.1+/-1.1 mU/l after 6 h (P<0.001 by ANOVA). Suppression of TSH secretion ranged from 30% to 60% of the baseline value. The T/nT ratio showed a trend toward a direct relationship with the degree of TSH inhibition after acute octreotide administration (r=0.67; P=NS). Our study showed that 111In-pentetreotide scan visualized somatostatin receptors in all five of the patients with TSH-secreting pituitary adenomas, confirming the frequent presence of somatostatin receptors in these rare tumours, even though the correlation with the TSH inhibition after a single administration of octreotide did not reach significance.     

Scintigraphic imaging of pituitary adenomas: an in vivo evaluation of somatostatin receptors

We have performed pituitary scintigraphy with the somatostatin (SS) analog pentetreotidean by (111In-P) in patients with GH-secreting adenoma or with "clinically non functioning" adenoma (NFA) to evaluate the presence and the functionality of SS receptors (SS-R). 111In-P pituitary accumulation was expressed as Activity Ratio (AR): the ratio between the uptake of radioactivity by the adenoma and that of the normal brain tissue. In subjects without pituitary disease, AR ranged from 1.6 to 2.2 and a value lower than 2.2 was thus arbitrarily considered as normal. In 15 out of the 17 patients with GH-secreting adenoma, an accumulation of the radioligand was shown. Median AR was 3.8 (range 1-6.9; in 14 AR were greater that 2.2) and ARs were directly correlated (r = 0.54; p < 0.05) with the suppressibility of plasma GH levels by octreotide (OC) acute administration. In two patients who repeated scintigraphy during chronic OC treatment, AR values were reduced. In all the 22 patients with NFA an accumulation of 111In-P at the pituitary level was observed and median AR was 3.0 (range 1.5-20; in 14 greater that 2.2). In vitro autoradiography of surgical specimens in 6 NFA patients revealed SS-R in 4 cases with high scintigraphic AR and negative results in two cases with low AR. Scintiscan was repeated during chronic OC treatment in 5 patients with high score: AR decreased in one patient, increased in three, and did not change in the other patient. No changes in tumor size were shown in any of these patients. A total of 8 patients (3 GH secreting and 5 NFA) had "normal" AR values. CONCLUSIONS: In acromegaly scintigraphy with 111In-P visualizes functioning pituitary SS-R coupled to intracellular events that control hormonal hypersecretion and tumor growth. In contrast, in spite of the positivity of 111In-P imaging in most patients with NFA, their receptors might have a defect in the coupling-transduction process, as they are not inhibited by OC treatment and no tumor shrinkage is observed.     

Radiolabeled somatostatin analog scintigraphy in differentiated thyroid carcinoma

After intravenous administration of a radiolabeled somatostatin analog (octreotide), an image of the thyroid gland is frequently observed; few data are available, however, on somatostatin receptors in epithelial thyroid cells assessed in vitro and on images of differentiated thyroid carcinoma (DTC) with pentetreotide scintigraphy. METHODS: In four patients with metastatic thyroid carcinoma, whole-body scintigraphy was performed 4 to 48 hr after injection of 110 MBq of 111In-pentetreotide. The results were compared to data obtained with other imaging modalities, including scintigraphy performed after administration of a therapeutic dose of 131I. RESULTS: There were positive foci in distant metastases on 111In-pentetreotide scintigraphy. Pentetreotide scintigraphy was positive in two patients with an "insular" form of DTC, one of whom had a positive (faintly) 131I scan. Of the other two patients with papillary DTC without radioiodine uptake, only one exhibited a certain degree of pentetreotide scintigraphy positivity in distant metastases. CONCLUSION: These results show promise for exploration of insular thyroid carcinoma and suggest that these carcinomas may possess functional differentiation features, including somatostatin receptors.     

Prediction of efficacy of octreotide therapy in patients with acromegaly

Octreotide (OCT) administration provides a biochemical cure in most acromegalic patients. This drug, however, causes several side effects and is very expensive. Acute testing has been reported to predict chronic responsiveness to OCT administration. The aim of this retrospective study was to evaluate which test, if any, among acute testing, short-term (1 month) administration, and 111In-pentetreotide (111In-DTPA-Phe-D-OCT) scintigraphy, is best in predicting response to long-term OCT treatment. Sixty-eight patients with active acromegaly were studied. An acute test (100 micrograms sc OCT) was performed as usual: a GH decrease greater than or equal to 50% of baseline was considered a positive response. GH and insulin-like growth factor I (IGF-I) were then assayed after 1 month (300 micrograms daily) and 3 months (150-600 micrograms daily) of OCT administration. GH was considered normalized when decreased less than or equal to 5 micrograms/L. Twenty-six of 68 patients were subjected to 111In-pentetreotide scintigraphy. Linear correlation analysis of the results was performed. Sensitivity, specificity, and positive and negative predictive values of the three tests were also calculated. Thirty-eight of 68 patients (56%) responded to the acute test. Among these 38 patients, 20 experienced normalization of GH and IGF-I levels during long-term therapy, as did 8 patients who did not respond to the acute test. No significant correlation was found between GH percent decrease during acute testing and long-term therapy (r = 0.11). Seven patients who responded to the acute test and 2 who did not respond had adenoma shrinkage during therapy. Conversely, GH and IGF-I decrease after short-term treatment significantly correlated with long-term treatment (r = 0.76 and 0.64, P < 0.01). Of the 26 patients subjected to 111In-pentetreotide scintigraphy, 13 had significant tracer uptake: normalization of GH and IGF-I was obtained in 8 patients. A significant correlation was found between tracer uptake and GH/IGF-I inhibition after 3 months of therapy (r = 0.6; P < 0.05). In the whole population, the positive predictive value of acute testing, short-term OCT administration, and 111In-penetreotide scintigraphy was 53%, 70%, and 73%, respectively, when the GH normalization (< 5 micrograms/L) after 3 months of therapy was considered. Moreover, 111-In-pentetreotide scintigraphy had the highest specificity (100% in patients with baseline GH values below 50 micrograms/L) compared with that of acute testing and short-term OCT administration. The acute test cannot be considered as a valuable index to identify patients' responsiveness to long-term OCT therapy, but it can be useful to test tolerability. By contrast, 1 month of OCT administration or the in vivo imaging of somatostatin receptors by 111-In-pentetreotide might better indicate the patients who might effectively benefit from this treatment.     

Radiolabeled somatostatin analog scintigraphy in oncology and immune diseases: an overview

[111In-DTPA-D-Phe1]-octreotide is a new radiopharmaceutical with a great potential for the visualization of somatostatin receptor-positive tumors, granulomas, and diseases in which activated leukocytes play a role. The overall sensitivity of [111In-DTPA-D-Phe1]-octreotide scintigraphy to localize neuroendocrine tumors is high. In several neuroendocrine tumor types, inclusion of somatostatin receptor imaging in the localization or staging procedure may be very rewarding, either in terms of cost-effectiveness, patient management, or quality of life. In our opinion, this holds true for patients with carcinoids, gastrinomas, paragangliomas, small-cell lung carcinoma, and selected cases of patients with insulinomas. The value of [111In-DTPA-D-Phe1]-octreotide scintigraphy in patients with other tumors, such as breast cancer, malignant lymphomas, or in patients with granulomatous diseases, has to be established.     

Pituitary adenomas: the role of 111In-DTPA-octreotide SPET in the detection of minimal post-surgical residues

Scintigraphy with 111In-DTPA-octreotide (111In-octreotide) enables the localization of tumours with somatostatin receptors on their cell membranes, of which pituitary adenomas are an example. Trans-sphenoidal excision of such tumours is sometimes incomplete and the detection of post-surgical residues is a difficult diagnostic task. In this study, we used 111In-octreotide SPET to visualize pituitary adenomas and their minimal residues. In positive cases, the indirect demonstration of the presence of somatostatin receptors may be decisive for the planning of treatment. 111In-octreotide SPET was able to visualize adenomas in 21 of 27 patients (77.7%) (10 GH-secreting, 10 PRL-secreting and 1 non-secreting). Repeat SPET after the recurrence of clinical symptoms and hormone hypersecretion revealed intense 111In-octreotide uptake by residues in 8 of 10 patients (4 GH-secreting and 6 PRL-secreting). Magnetic resonance imaging was positive in only 3 of these 10 patients. Our results suggest that 111In-octreotide SPET, in combination with other imaging modalities, is useful in the diagnosis and follow-up pituitary adenomas. It ensures better selection of patients for treatment with somatostatin analogues, both pre- and post-operatively, and assists in the development of personalized treatment plans.     

Indications and limits of ultrasound-guided cytology in the management of nonpalpable thyroid nodules

PURPOSE: This report illustrates the potential diagnostic and therapeutic utility of somatostatin receptor scintigraphy and therapy with somatostatin. METHODS: In-111 pentetreotide (In-111 octreotide), a somatostatin analog, was used to define the receptor status and the extent of disease in a case of malignant thymoma. RESULTS: Subsequent treatment with nonradioactive somatostatin inhibited tumor growth. CONCLUSION: In-111 octreotide may be useful to define tumor receptor status and may provide prognostic information useful in determining subsequent therapy.     

Somatostatin receptor imaging in patients with sarcoidosis

Granulomatous diseases can be visualized in vivo after the injection of indium-111-DTPA-octreotide (111In-pentetreotide), a radiolabelled somatostatin analogue. We evaluated whether somatostatin receptor imaging reflects disease activity, whether certain scintigraphic characteristics can predict the disease prognosis and whether repeat scintigraphy correlates with the clinical course in patients with sarcoidosis. 111In-pentetreotide was injected in 46 patients and images were obtained 24 h later. Known mediastinal, hilar and interstitial disease was recognized in 36 of 37 patients. Also, such pathology was found in seven other patients who had normal chest X-rays. In five of these, somatostatin receptor imaging pointed to interstitial disease. Frequently, accumulation of radioactivity in parotid glands and supraclavicular lymph nodes was found. Neither the degree of radioactive accumulation in the thorax nor a specific pattern of pathological uptake was correlated with disease severity or clinical course. The degree of uptake of radioactivity in the parotid glands was correlated with significantly higher serum angiotensin-converting enzyme (ACE) levels. Somatostatin receptor imaging was repeated in 13 patients. In five of six patients in whom chest X-ray monitored improvement of disease activity, the pentetreotide scintigram also showed a decrease in pathological uptake. In two of five patients in whom the chest X-ray was unchanged, but serum ACE concentrations had decreased and lung function improved, normalization on pentetreotide scintigrams was found. It is concluded that: (1) somatostatin receptor imaging can demonstrate active granulomatous disease in patients with sarcoidosis; (2) pathological uptake of radioactivity in the parotid glands during somatostatin receptor imaging is correlated with higher serum ACE concentrations; (3) the value of somatostatin receptor imaging in the follow-up of patients with sarcoidosis will have to be determined in a prospective longitudinal study.     

Increased density of I2-imidazoline receptors in human glioblastomas

A glial location has been proposed for the non-adrenoceptor [3H]idazoxan binding site termed the I2-imidazoline receptor. The specific binding of [3H]idazoxan in the presence of (-)adrenaline was measured in membranes from excised human glioblastomas (n = 6), meningiomas (n = 6) and normal brains (n = 6). The pharmacological profile of the [3H]idazoxan binding in astrocytic tumours was similar to that in normal brain, compatible with the presence of I2-imidazoline receptors. There was a higher density of I2-imidazoline receptors in astrocytic tumours (Bmax = 266 +/- 18 fmol mg-1 protein; p < 0.001) than in normal brain (Bmax = 54 +/- 4 fmol mg-1 protein), with no differences in affinity values. Almost no [3H]idazoxan-specific binding was shown in meningiomas. The results suggest that I2-imidazoline receptors may be a selective marker for glial tumours in the evaluation of intracranial neoplasms.     

Somatostatin receptors in meningioma: diagnostic and therapeutic value

OBJECTIVE: We discuss the diagnostic and therapeutic usefulness of the presence of somatostatin receptors (SR) in meningiomas. DEVELOPMENT: The SR are membrane receptors, may be saturated, have great affinity and pharmacological specificity for somatostatin (SS) and its analogues. SR have been found in 100% of the meningiomas studied. The presence of a large number of SR in different tumours permits gammagraphic detection in vivo by marking SS analogues with 1-231-DTPA and subsequent visualization using a gamma camera. This study may help to differentiate between meningiomias and other tumour lines. Experiments using different SS analogues have shown different degrees of affinity of these SS analogues for the different receptors. In various animal models a potent inhibitor effect on tumour growth has been seen following SS and its analogues. Unlike in hypophyseal adenomas and endocrine gastro-entero-pancreatic tumours, neither SS nor its analogues have shown any direct inhibitory action on the growth of meningioma cell cultures. Quite the opposite occurs. A small but significant stimulation of growth was seen in the presence of SS. CONCLUSIONS: We consider the detection of SR by isotopic marking of SS analogues is useful in the differential diagnosis of meningiomas. The therapeutic usefulness of the analogues of SS for treatment of meningiomas remains controversial. Further study of the different types of receptors and analogues is necessary.     

Somatostatin receptors. A new way to diagnosis and therapy of neuroendocrine tumors

Verification of the presence of somatostatin receptors on neuroendocrine tumour cells opened up unique diagnostic and therapeutic possibilities. Long-acting somatostatin analogues are currently used to alleviate symptoms of excessive hormone synthesis in patients with such tumours. Radiolabelled somatostatin analogues can be used both for high specificity and high sensitivity scintigraphic localisation of such tumours and for intraoperative scintillation detection. Detailed studies in patients and in tumour cells in vitro have shown 111In-octreotide uptake to be high and retention times long in tumour tissue, and have yielded evidence of intracellular localisation of the radionuclide. These findings thus showed somatostatin receptor-mediated radiotherapy to be a possible treatment alternative after close characterisation of the individual tumour. In the future, it may be possible to use other peptide receptors (e g, growth factor receptors) according to the same principles as applied in the case of somatostatin receptors.     

Comparison of metabolic and receptor imaging in recurrent medullary thyroid carcinoma with histopathological findings

Early diagnosis of metastases of medullary thyroid carcinoma (MTC) provides the optimal condition for curative outcome. The aim of this study was to appraise the detection of metastases in patients with recurrent MTC using [111In-DTPA-d-Phe1]-pentetreotide and pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] in comparison with histopathological findings. Eighteen MTC patients with persistently elevated tumour marker (calcitonin, carcinoembryonic antigen) levels underwent somatostatin receptor scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide (222 MBq) with early (4 h after injection) and delayed (24 h) whole-body scans and single-photon emission tomography (SPET) imaging. Metabolic whole-body and SPET imaging using 500 MBq 99mTc(V)-DMSA was performed 4 h after injection. Metabolic and receptor imaging revealed 51 sites of focal accumulation in the 18 patients investigated. Comparison with histological findings revealed that metabolic and receptor imaging had a sensitivity of 84% for the diagnosis of MTC. Using [111In-DTPA-d-Phe1]-pentetreotide, SPET discovered four lymph node metastases in two patients in whom planar views had previously identified only one lymph node metastasis, and provided no new information in the other 16 patients. In comparison, SPET studies [using 99mTc(V)-DMSA] additionally localized eight lymph node metastases in four patients and confirmed the diagnosis of hepatic metastases (n=5) in another patient in whom conventional imaging modalities and planar views had previously detected only three liver metastases. Overall, lesion detection sensitivities for 99mTc(V)-DMSA and [111In-DTPA-D-Phe1]-pentetreotide were 69% and 29%, respectively. Five surgically removed foci were adjudged false-positive with respect to MTC metastases. False-positve results were caused by lymphadenitis, an enchondroma and a pheochromocytoma (histologically proven). The smallest lesion identified by metabolic imaging was a 6 mm in diameter lymph node metastasis located in the upper mediastinum. Somatostatin receptor scintigraphy only demonstrated tumour sizes more than 1 cm in diameter. These preliminary results suggest that the combination of metabolic [99mTc(V)-DMSA] and receptor ([111In-DTPA-D-Phe1]-pentetreotide) imaging is more sensitive for tumour localization in patients with recurrent MTC than the use of only one radiopharmaceutical. However, neither 99mTc(V)-DMSA nor [111In-DTPA-D-Phe1]-pentetreotide is specific for MTC and false-positive scintigraphic findings have to be considered. Furthermore, somatostatin receptor scintigraphy cannot visualize small tumour sites (<1 cm). Further studies are needed to evaluate the role of combined metabolic and receptor imaging in the management of patients with recurrent MTC.     

Spasskyellina mandi n. sp. (Proteocephalidea:Monticelliidae), parasite of Pimelodus ornatus Kner, 1857 (Pisces:Pimelodidae) of the Paraná River, Paraná, Brazil

Indium-111 pentetreotide scintigraphy was performed in two patients for the localization of recurrent medullary thyroid carcinoma treated by surgery and external radiotherapy 1 and 10 years earlier. A marked uptake of the radiopharmaceutical was demonstrated in the lung areas that had been irradiated. These cases strongly suggest that this uptake is related to pulmonary fibrosis, a well-known complication of radiotherapy, even long after the irradiation. Therefore, attention must be paid to the avoidance of false-positive interpretation of somatostatin receptor scintigraphy in patients previously treated by radiotherapy.