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  • 1
    Electronic Resource
    Electronic Resource
    Expression of Somatostatin Receptors in Normal, Inflamed, and Neoplastic Human Gastrointestinal Tissues (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 733 (1994), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1994.tb17262.x
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  • 2
    Electronic Resource
    Electronic Resource
    Somatostatin and Thyrotrophin-Releasing Hormone Response and Receptor Status of a Thyrotrophin-Secreting Pituitary Adenoma: Clinical and in vitro Studies (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neuroendocrinology 1 (1989), S. 0 
    Details
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have described a patient with a thyrotrophin-secreting pituitary adenoma and correlated a detailed physiological and anatomical investigation of the surgically resected tumour with its in vivo regulation. Thyrotrophin secretion was inhibited by circulating thyroid hormones, dopaminergic agonists and the somatostatin analogue SMS 201–995 but could not be stimulated by thyrotrophin-releasing hormone or further inhibited by exogenous triiodothyronine. Prolonged treatment with SMS 201–995 caused tumour shrinkage as shown by successive computed tomography scans but was accompanied by tumour desensitization and the development of diabetes mellitus. This is the first thyrotroph adenoma in which somatostatin receptors have been directly demonstrated and shown to completely block thyrotrophin-releasing hormone-induced inositol phospholipid accumulation when occupied. In addition, preincubation with triiodothyronine significantly inhibited thyrotrophin-releasing hormone-induced inositol phospholipid turnover in dispersed pituitary cells indicating that in this tumour, circulating thyroid hormones were exerting feedback inhibition at the level of the pituitary either by reducing the number of thyrotrophin-releasing hormone receptors and/or their coupling to second messenger pathways. In keeping with this hypothesis, the acute reduction in intrapituitary triiodothyronine by sodium ipodate in vivo had no effect on peripheral thyrotrophin over 6 h suggesting that the onset of the effect of triiodothyronine withdrawal on thyrotrophin secretion was suitably delayed. The importance of the inositol phospholipid second messenger pathway in transducing the secretory response in this tumour was further corroborated by electrophysiological studies which demonstrated thyrotrophin-releasing hormone-induced changes in K+ currents which are dependent on intracellular Ca2+ ions, presumably mobilized via the inositol phospholipids. In addition to thyrotrophin and α subunit, growth hormone mRNA and growth hormone were found throughout the tumour as were two populations of cells distinguished electron microscopically by the size of their secretory granules. Although acromegalic features are not unusual in thyrotroph adenomas, our patient showed no evidence of inappropriate growth hormone secretion during surgery or in response to pre- or post-operative insulin stress tests.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2826.1989.tb00123.x
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  • 3
    Electronic Resource
    Electronic Resource
    In Vitro Identification of VIP Receptors in Human Tumors: Potential Clinical Implications (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 805 (1996), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1996.tb17553.x
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  • 4
    Electronic Resource
    Electronic Resource
    The value of octreotide scintigraphy in patients with lung cancer (1994)
    Springer
    European journal of nuclear medicine 21 (1994), S. 1106-1113 
    Details
    ISSN: 1619-7089
    Keywords: Somatostatin ; Octreotide ; Lung carcinoma ; Small cell lung carcinoma ; Scintigraphy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated octreotide scintigraphy in 81 untreated patients who were suspected of having bronchial carcinoma. Octreotide scintigraphy visualized the primary tumour in all of 40 patients with non-smallcell lung carcinoma (non-SCLC), and all of 26 patients with SCLC. In the remaining patients, other bronchial disease and metastases from extrapulmonary carcinomas were also visualized. Mediastinal lymph node involvement and distant metastases were recognized in 5 of 15 and 1 of 7 patients with non-SCLC, respectively. In vitro, none of the non-SCLCs were shown to bear somatostatin receptors. We postulate that the visualization of non-SCLC during octreotide scintigraphy is caused by binding of labelled octreotide to activated leucocytes or to proliferating neuroendocrine cells around the tumours. In patients with SCLC, radiologically suspected lymph node involvement was visualized for 21 of 25 sites. Distant metastases, especially to the liver and abdomen, were missed for 14 of 20 sites, most probably because no laxatives were administered and single photon emission tomography of the abdomen was not performed. The failure to recognize liver metastases is most probably due to a comparable uptake of radioactivity by the surrounding normal liver tissue. In 15 of 26 patients, previously unrecognized tumour sites were suggested during octreotide scintigraphy, leading to a downstaging of 5 of 14 patients with limited disease. Unexpected cerebral metastases were suggested in five patients with either limited or extensive disease. In all four of these for whom follow-up was available, cerebral metastases became manifest 5–8 months after octreotide scintigraphy. We conclude (1) that octreotide scintigraphy is of no use to differentiate SCLC from other lung disease, and (2) that octreotide scintigraphy should be included in the staging procedure of SCLC because it may allow early detection of metastases, especially to the brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00181066
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  • 5
    Electronic Resource
    Electronic Resource
    Vasoactive intestinal peptide receptor scintigraphy in patients with pancreatic adenocarcinomas or neuroendocrine tumours (2000)
    Springer
    European journal of nuclear medicine 27 (2000), S. 1684-1693 
    Details
    ISSN: 1619-7089
    Keywords: Vasoactive intestinal peptide Receptor scintigraphy Pancreatic adenocarcinoma Neuroendocrine tumours
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Human adenocarcinomas of the gastroenteropancreatic system overexpress vasoactive intestinal peptide (VIP) receptors and therefore represent logical diagnostic targets for receptor scintigraphy. Using iodine-123 labelled VIP, the newly employed diagnostic procedure termed VIP receptor scintigraphy (VIP-RS) appears to detect tumour tissue, especially pancreatic metastatic tumours, in almost all cases. So far, however, only a single centre has demonstrated convincing positive results. The aim of this study was to compare the sensitivity and specificity of VIP-RS with those of computer tomography (CT) and transabdominal ultrasound in patients with extensive pancreatic metastatic adenocarcinomas and neuroendocrine tumours. VIP was radiolabelled with carrier-free 123I using the chloramine T-method and preparative high-performance liquid chromatography for purification. Patients with metastatic pancreatic (n=12) and colorectal (n=3) carcinomas (adenocarcinoma: n=13, neuroendocrine tumour: n=2) were studied by VIP-RS, CT, ultrasound and, in one case, also by radioligand receptor autoradiography. Carrier-free radioiodinated VIP of maximum specific radioactivity maintained a high biological activity as determined by cAMP formation in receptor-expressing tumour cell lines. Intravenous injection of 123I-VIP did not cause any side-effects. Biodistribution, determined over 24 h, was high in the lungs and low in abdominal organs. Although all patients had extensive metastatic disease as evidenced by CT and ultrasound, VIP-RS was unable to detect either primaries or metastases in these patients. Only in two patients could a significant uptake of radiolabel be detected in organs directly infiltrated by the primary. To exclude false-negative findings, tumour tissue in one patient with a large primary, undetectable by VIP-RS, was analysed by radioligand receptor autoradiography and shown to be receptor positive. Moreover, in vitro receptor determinations showed that pancreatic carcinomas usually have fewer VIP receptors than the normal tissues to which they metastasize, like the liver. It is concluded that VIP can be radioactively labelled with maximum specific radioactivity while maintaining biological activity. Intravenous administration leads to a biodistribution almost identical to that reported previously. However, in contrast to these reports, very low sensitivity and specificity were observed for the detection of pancreatic cancers. In retrospect, these findings are not surprising since VIP receptor expression was observed to be higher in normal tissues than in neoplastic ones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002590000325
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  • 6
    Electronic Resource
    Electronic Resource
    Affinity profiles for human somatostatin receptor subtypes SST1–SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use (2000)
    Springer
    European journal of nuclear medicine 27 (2000), S. 273-282 
    Details
    ISSN: 1619-7089
    Keywords: Key words: Somatostatin receptor subtypes – Receptor affinity – Gallium-labelled radioligands – Yttrium-labelled radioligands – Octreotate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. In vivo somatostatin receptor scintigraphy using Octreoscan is a valuable method for the visualisation of human endocrine tumours and their metastases. Recently, several new, alternative somatostatin radioligands have been synthesised for diagnostic and radiotherapeutic use in vivo. Since human tumours are known to express various somatostatin receptor subtypes, it is mandatory to assess the receptor subtype affinity profile of such somatostatin radiotracers. Using cell lines transfected with somatostatin receptor subtypes sst1, sst2, sst3, sst4 and sst5, we have evaluated the in vitro binding characteristics of labelled (indium, yttrium, gallium) and unlabelled DOTA-[Tyr3]-octreotide, DOTA-octreotide, DOTA-lanreotide, DOTA-vapreotide, DTPA-[Tyr3]-octreotate and DOTA-[Tyr3]-octreotate. Small structural modifications, chelator substitution or metal replacement were shown to considerably affect the binding affinity. A marked improvement of sst2 affinity was found for Ga-DOTA-[Tyr3]-octreotide (IC50 2.5 nM) compared with the Y-labelled compound and Octreoscan. An excellent binding affinity for sst2 in the same range was also found for In-DTPA-[Tyr3]-octreotate (IC50 1.3 nM) and for Y-DOTA-[Tyr3]-octreotate (IC50 1.6 nM). Remarkably, Ga-DOTA-[Tyr3]-octreotate bound at sst2 with a considerably higher affinity (IC50 0.2 nM). An up to 30-fold improvement in sst3 affinity was observed for unlabelled or Y-labelled DOTA-octreotide compared with their Tyr3-containing analogue, suggesting that replacement of Tyr3 by Phe is crucial for high sst3 affinity. Substitution in the octreotide molecule of the DTPA by DOTA improved the sst3 binding affinity 14-fold. Whereas Y-DOTA-lanreotide had only low affinity for sst3 and sst4, it had the highest affinity for sst5 among the tested compounds (IC50 16 nM). Increased binding affinity for sst3 and sst5 was observed for DOTA-[Tyr3]-octreotide, DOTA-lanreotide and DOTA-vapreotide when they were labelled with yttrium. These marked changes in subtype affinity profiles are due not only to the different chemical structures but also to the different charges and hydrophilicity of these compounds. Interestingly, even the coordination geometry of the radiometal complex remote from the pharmacophoric amino acids has a significant influence on affinity profiles as shown with Y-DOTA versus Ga-DOTA in either [Tyr3]-octreotide or [Tyr3]-octreotate. Such changes in sst affinity profiles must be identified in newly designed radiotracers used for somatostatin receptor scintigraphy in order to correctly interpret in vivo scintigraphic data. These observations may represent basic principles relevant to the development of other peptide radioligands.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002590050034
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  • 7
    Electronic Resource
    Electronic Resource
    Cholecystokinin receptor imaging using an octapeptide DTPA-CCK analogue in patients with medullary thyroid carcinoma (2000)
    Springer
    European journal of nuclear medicine 27 (2000), S. 1312-1317 
    Details
    ISSN: 1619-7089
    Keywords: Cholecystokinin Peptide receptor imaging CCK receptor Medullary thyroid carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Cholecystokinin (CCK)-B receptors have been demonstrated on a high percentage of medullary thyroid carcinomas (MTC) in vitro. After encouraging results both in vitro and in animal studies, we studied the efficacy of an octapeptide [111In-DTPA]-CCK analogue in seven patients with MTC. In four of five patients in whom serum calcitonin levels were monitored, a significant rise was found following the injection, indicating retained biological activity of the radiopeptide. In all patients there was visualization of the CCK-B receptor-positive stomach. In one of two patients with known MTC lesions, some of the lesions were visualized; in addition some lesions were visualized in one of the five other patients who had elevated serum tumour markers but negative localizing studies. Radioactivity in the presumed tumour sites was still present at 48 h p.i. The uptake in the presumed tumour sites and stomach was low. Background radioactivity dropped rapidly owing to urinary excretion. After 1 h, breakdown products of the labelled analogue predominated both in urine and in serum, and virtually no intact peptide was present. In conclusion: (1) the CCK-B receptor-positive gastric mucosa and presumed MTC lesions could be visualized in patients using an octapeptide [111In-DTPA]-CCK analogue that is probably internalized, proving the feasibility of CCK-B receptor imaging in vivo; (2) there was a relatively low uptake of the CCK analogue in the strongly CCK receptor-positive stomach, and rapid degradation of the peptide in serum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002590000296
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