Unlabelled somatostatin analogues in treatment of digestive endocrine tumours

Panzuto, Francesco; Nasoni, S.; Baccini, Flavia; Cassetta, S.; Corleto, V.D.; Fave, Gianfranco Delle

doi:10.1016/j.dld.2003.11.013

Cited by 4 publications

(4 citation statements)

References 37 publications

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“…Several studies have shown that SSTR subtypes 1 and 2 are those most highly expressed in GEP tumours [8,9,10,11,12]. However, multiple SSTR subtype expression, and a limited in vivo antigrowth effect of the currently available SSTR analogues, account for their relatively low or complete lack of efficacy on tumour growth control [2, 3]. …”

Section: Introductionmentioning

confidence: 99%

“…Native somatostatin binds with high affinity to all somatostatin subtypes, whereas octreotide and other available cyclic analogues bind with the highest affinity to SSTR2, with high affinity to SSTR5 and SSTR3 and with low affinity to SSTR4 and SSTR1. Direct therapeutic inhibition of hormonal secretion in the functioning tumour and/or an indirect effect on the inhibition of growth factors may help to stabilize tumour growth in ∼70% of treated patients [2, 3, 6, 7]. SSTR have been extensively studied in human endocrine and non-endocrine gastrointestinal tumours.…”

Section: Introductionmentioning

confidence: 99%

“…Given the higher expression of somatostatin receptor (SSTR) subtypes in these tumours compared to normal tissues, somatostatin analogues represent first-line treatment for ∼90% of GEP tumours [1,2,3]. …”

Section: Introductionmentioning

confidence: 99%

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Somatostatin Receptor Subtypes 2 and 5 Are Associated with Better Survival in Well-Differentiated Endocrine Carcinomas

Corleto

Falconi²,

Panzuto

et al. 2008

Neuroendocrinology

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The majority of gastroenteropancreatic well-differentiated endocrine carcinomas (WDEC) express somatostatin receptors (SSTR). To correlate the expression of SSTR subtypes by reverse transcriptase-polymerase chain reaction (RT-PCR) with clinicopathological features and survival in a group of WDEC patients, 42 WDEC tissue specimens from 33 patients were analysed. All patients were treated with somatostatin analogues and had a median follow-up period of 45 months (range 6–196). Neither SSTR2 and SSTR5 expression nor Ki-67 level alone correlated with survival. A significantly better survival rate was observed in patients with tumours expressing SSTR2, SSTR5 and Ki-67 <2%, compared to those with SSTR2– and SSTR5–negative tumours and Ki-67 ≥2% (p < 0.038), with 5-year survival rates of 91 vs. 43%, respectively. Expression of SSTR2 and SSTR5 appears to play a positive prognostic role, possibly correlated with the high affinity that the available somatostatin analogues display for these 2 specific SSTR subtypes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Somatostatin Receptor Subtypes 2 and 5 Are Associated with Better Survival in Well-Differentiated Endocrine Carcinomas

Corleto

Falconi²,

Panzuto

et al. 2008

Neuroendocrinology

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“…sstrs are in fact widely distributed in many organs, such as the pancreas and pituitary gland, and in tumors arising from these and other organs [4,5,6,7,8,9,10,11]. The majority of NET express sstrs with a high density and in different combinations [10,12,13,14,15], thus making SSAs a first-line treatment for the relief of symptoms associated with functioning NET [16,17,18,19,20,21,22,23,24]. …”

Section: Introductionmentioning

confidence: 99%

Monoclonal Antibodies against the Human Somatostatin Receptor Subtypes 1–5: Development and Immunohistochemical Application in Neuroendocrine Tumors

et al. 2011

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Background: Activation of somatostatin receptors (sstr1–5) by somatostatin and its analogues exerts an inhibitory effect on hormone secretion and provides the basis for the treatment of a range of endocrine diseases such as acromegaly, Cushing’s disease and neuroendocrine tumors (NET). The lack of well-characterized commercially available sstr subtype-specific antibodies prevents routine identification of the sstr expression profile in patients. Methods: We generated and characterized new mouse monoclonal antibodies (mAbs) targeting the five human sstr subtypes using ELISA and immunohistochemistry, and tested their suitability in formalin-fixed and paraffin-embedded (FFPE) human tissues and archival samples of normal pancreatic tissue and NET. Results: All mAbs were highly specific with no cross-reactivity. The sstr1–5 immunoreactivity in gastrointestinal NET (n = 67) was correlated with clinicopathologic data. With the exception of sstr3, NET were highly positive for all receptor subtypes (42, 63, 6, 32 and 65% of tumors were positive for sstr1, sstr2a, sstr3, sstr4 and sstr5, respectively). sstr1, sstr2a and sstr5 were present at the plasma membrane and in the cytoplasm of tumor cells, whereas sstr3 and sstr4 were almost exclusively cytoplasmic. Immunoreactivity of sstr1, sstr2a and sstr4 tended to decrease as tumor aggressiveness increased. sstr5 showed an opposite pattern, with higher staining in well-differentiated carcinomas compared with well-differentiated tumors. sstr5 immunoreactivity was correlated with the presence of metastases and angioinvasion, suggesting a possible association with more aggressive behavior. Conclusion: Determination of the sstr1–5 by immunohistochemistry using subtype-specific mAbs is feasible in FFPE tissue and may provide a tool for routine clinical practice.

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Preparo do reagente liofilizado HYNIC-[Tyr3]-Octreotato e estudo de marcação com Tecnécio-99m

Melo¹

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The development of radiolabeled molecules with high specificity for an organ or tumor has been contributed to the precise diagnostic in nuclear medicine. Somatostatin labeled derivatives constitutes a particular example of labeled peptide applied in the localization of neuroendocrine tumors. Nowadays, the 111 In-DTPA-octreotideo is the radiopharmaceutical applied in diagnostic procedures for the visualization of tumors with high expression of somatostatin receptors. However, the 111-indium is a radionuclide that presents some limitations related to availability (cyclotron production), half-life (67 hours) and the emission of medium energy photons (171 keV e 245 keV), not favorable to the acquisition of images in SPECT (Single Photon Emission Computed Tomography). The favorable physical properties of the 99m-technetium (99m Tc) make this radionuclide the more favorable to substitute the 111-indium on peptide labeling procedures. This work studied the preparation and labeling of a lyophilized kit of HYNIC-Tyr 3-octreotate (HYNIC-octreotate) with 99m Tc, base on previously described procedures and using tricine and EDDA (ethylendiaminediacetic acid) as coligands. It was studied the labeling parameters (incubation time, temperature, volume and perthecnetate activity) and the stability of the lyophilized preparation. Additionally, it was studied the influence of the pre-freezing using liquid nitrogen in the stability of the lyophilized preparation, as well as the influence of manitol in the labeling yield and biological distribution of the complex. The stability studies showed that the lyophilization using liquid nitrogen pre-freezing resulted in a lyophilized preparation with stability over 4 month when stored under refrigeration. The stability of the lyophilized preparation obtained without liquid nitrogen pre-freezing was similar.The labeling studies determined the best labeling conditions, resulting in a radiochemical yield superior than 90%. The use of manitol in the formulation did not influence the formation of the complex 99m Tc-HYNIC-Octreotate, as evidenced in HPLC and in the scintigraphic studies of the complex biodistribution in rabbits. Invasive biodistribution studies using xenographed Nude mice (pancreatic tumor cells AR42J) and healthy Swiss mice, and scintigraphic studies in rabbits showed the fast kinetic distribution, renal uptake and significative tumoral uptake of the labeled peptide. The results of labeling studies with 99m Tc, the production of the lyophilized kit and the biodistribution studies suggest that the 99m Tc-HYNIC-Octreotate is a potential radiopharmaceutical to be applied in the diagnostic of neuroendocrine tumors in nuclear medicine.

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Unlabelled somatostatin analogues in treatment of digestive endocrine tumours

Cited by 4 publications

References 37 publications

Somatostatin Receptor Subtypes 2 and 5 Are Associated with Better Survival in Well-Differentiated Endocrine Carcinomas

Somatostatin Receptor Subtypes 2 and 5 Are Associated with Better Survival in Well-Differentiated Endocrine Carcinomas

Monoclonal Antibodies against the Human Somatostatin Receptor Subtypes 1–5: Development and Immunohistochemical Application in Neuroendocrine Tumors

Preparo do reagente liofilizado HYNIC-[Tyr3]-Octreotato e estudo de marcação com Tecnécio-99m

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