Somatostatin receptor scintigraphy in thoracic diseases

Abstract

Somatostatin (SS) receptor scintigraphy is useful for the diagnosis of lesions with high density of SS receptors, and above all neuroendocrine tumors. For several years, only indium-labeled octreotide has been applied to visualise in vivo tissues with SS receptor overexpression. Radiolabeled octreotide became the gold standard for the detection of neuroendocrine tumors. More recently, however, several new SS analogues with varying affinity for SS receptor subtypes have been developed, and different radionuclides as radiolabels have been introduced. Moreover, significant improvements have been made by the introduction of hybrid machines, such as single photon emission computed tomography/ computed tomography (SPECT/CT) or positron emission tomography (PET)/CT that enable to perform whole-body imaging quickly and with high anatomical resolution in several body areas, including the chest. The development of more specific radiopharmaceuticals, together with the modern technique of imaging, may provide excellent quality images with high contrast, allowing to depict very small lesions and making them easy to interpret. Indeed, in the management of SS receptor-positive lesions, the contribution of nuclear medicine is essential in several clinical settings, such as initial diagnosis, disease staging, follow-up, treatment planning, and treatment monitoring. In addition, the tracer uptake might be used as a prognostic parameter and as a predictor of treatment response. In the chest, apart in (neuro)endocrine tumors, SS receptors have been demonstrated in granulomatous diseases, like sarcoidosis and other immune-mediated disorders, such as anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. In this paper we review and discuss the role of SS receptor scintigraphy in diagnosis, staging or follow- up of thoracic SS receptor-positive lesions.

The role of somatostatin and dopamine D2 receptors in endocrine tumors

“…Moreover, a number of malignancies arising from immune cells, such as Hodgkin disease, T and B non-Hodgkin lymphomas (Reubi et al 1992d, Lugtenburg et al 2001a, myeloma, and plasmacytoma (Georgii-Hemming et al 1999, Duet et al 2005 heterogeneously express SSTR, although the role of SSTR targeting for diagnosis or treatment in these tumors is still debated. Finally, a clear positivity by SSTR scintigraphy has been observed in a number of chronic inflammatory diseases, such as sarcoidosis (van Hagen et al 1994, Ameri et al 2007) and rheumatoid arthritis (ten Bokum et al 1999).…”

Small Cell Lung Cancer in an Elderly Patient: Efficacy of Somatostatin Analog Treatment, a Case Report

“…IthasbeendemonstratedbyinvitrostudiesthatNETsofthe lungcanoverexpressseveralpeptidereceptors:somatostatin receptors(SSTRs)arethemostcommon,althoughotherpeptides have been reported less frequently, such as vasoactive intestinalpeptide(VIP),cholecystokinin(CCK),neurotensin, bombesin/gastrin-releasingpeptide,atrialnatriureticpeptide (ANP), calcitonin and calcitonin gene-related peptide (CGRP), oxytocin, and glucagon-like peptide-1 [6]; these findingshavebeenconfirmedinvivobyOctreoscan ® evaluation and immunohistochemistry [7]. In the chest, besides inNETs,SSTRhavealsobeendemonstratedingranulomatous diseases, like sarcoidosis and other immune-mediated disorders such as anti-neutrophil cytoplasmic antibody (ANCA)-associatedvasculitis [8].Theirexpressionwasoccasionallydemonstratedinnon-smallcelllungcancer(NSCLC) [9].Theactivityof somatostatin(SS)isduetoitsinteraction withafamilyoftransmembranereceptors,theSSTRfamily, including 5 different G-protein-coupled receptors (from SSTR1toSSTR5).Recently,severalpeptideslikeoctreotide or lanreotide have been discovered, with similar binding affinityasSStoitsreceptorsandsimilaractivity [10].Those derivatives of somatostatin are effective in the secretory regulationofNETcells;however,theyhavebeendisappointing as antiproliferative agents in vivo for gastrointestinal carcinoids [11];incontrast,invitroexperimentshaveshown effective inhibition of cell proliferation in lung NETs by somatostatin analogs [12], although there are only few and non-conclusiveclinicalreports [13,14].Anotherclinicaluseof SS analogs is related to the possibility of visualizing SSTRpositive tumors and mapping their localizations by injecting labeledpeptides [15]. According to the World Health Organization (WHO) criteria [1],pulmonaryNETsdonotconstituteasingle,uniform entity but are considered as a spectrum of differently differentiatedlesionsassociatedwithspecificpathologicalfeaturesandwithavariableclinicalbehavior.Typicalcarcinoids andatypicalcarcinoidsaswellaspoorlydifferentiatedtypes, such as large-cell neuroendocrine carcinoma and small cell lung cancer (SCLC), were identified.…”

Diffuse Endocrine System, Neuroendocrine Tumors and Immunity: What’s New?

“…This modulation seems to be relevant in humans too, since in more than 300 children serum levels of SRIH and VIP have been associated with circulating Th2 cytokines, expression of Th2 transcription factors in T cells, and allergic sensitization [45]. Exploiting the potential of some neuropeptides of determining a Th2 bias might be of value to treat Th1-driven autoimmune processes, such as sarcoidosis [13], multiple sclerosis [46], Crohn’s disease, and rheumatoid arthritis [32]. In animal models of the latter two, CST selectively inhibited the release of Th1 cytokines by CD4+ lymphocytes infiltrating the colon or joints, respectively, and the draining lymph nodes, without affecting the levels of the Th2 signature cytokine IL-4 [29,30].…”

“…For instance, human monocytes do not transcribe any SSTR gene in resting conditions, but express SSTR2A when activated with lipopolysaccharide, and both SSTR1 and SSTR2A when induced to differentiate into macrophages or DCs [7,8,9]. In vivo, SSTR2A is present on the membrane of macrophages and DCs [5,11,12], making tissues physiologically or pathologically rich of SSTR2A detectable by SSTR scintigraphy with radiolabelled somatostatin (SRIH) analogs having high affinity for SSTR2A, such as the routinely used 111 In-pentetreotide (Octreoscan®) [12,13]. …”

“…As exemplified by somatostatin receptors (SSTR) 1–5 (fig. 1) [5,6,7,8,9,10,11,12], the expression profile of many neuropeptide receptors varies across different types of immune cells, and changes upon their differentiation or activation status, further pointing to a fine regulation of immunity by neuropeptides [13]. For instance, human monocytes do not transcribe any SSTR gene in resting conditions, but express SSTR2A when activated with lipopolysaccharide, and both SSTR1 and SSTR2A when induced to differentiate into macrophages or DCs [7,8,9].…”