Somatostatin Receptor Subtype 2 Is Expressed by Supratentorial Primitive Neuroectodermal Tumors of Childhood and Can Be Targeted for Somatostatin Receptor Imaging

Abstract

Purpose: Although gliomas predominate among central nervous system (CNS) neoplasms in adulthood, embryonal tumors are the most common malignant brain tumors in children. Despite novel treatment approaches, including improved radiotherapy and high-dose chemotherapy, survival rates remain unsatisfactory. The timely diagnosis of residual or recurrent embryonal CNS tumors and thus the earliest possible time point for intervention is often hampered by inaccuracies of conventional imaging techniques. Novel and refined imaging methodologies are urgently needed.Experimental Design: We have previously demonstrated the use of somatostatin receptor imaging (SRI) in the diagnosis of recurrent and residual medulloblastomas. Here, we evaluated somatostatin receptor type 2 (sst 2 ) expression using an antibody in an array of CNS tumors of childhood. Eight high-grade gliomas, 4 atypical teratoid/rhabdoid tumors, 7 supratentorial primitive neuroectodermal tumors (stPNET), 1 medulloepithelioma (ME), and 8 ependymomas were screened. Tumors positive in vitro were additionally analyzed in vivo using SRI.Results: Abundant expression of somatostatin receptor type 2 in stPNET, a ME, and ependymomas warranted in vivo imaging of 7 stPNET, 1 rhabdomyosarcoma, 3 ependymomas, 1 ME, and 1 glioblastoma. Although SRI was positive in 6/7 stPNET, 1 rhabdomyosarcoma, and 1 ME, none of the ependymomas nor the glioblastoma could be imaged using SRI. In selected cases SRI was more sensitive in the detection of relapse than conventional imaging by magnetic resonance imaging and computed tomography.Conclusions: SRI should be considered in the evaluation of residual or recurrent embryonal CNS tumors, especially stPNET. The strengths of SRI lie in the differentiation of reactive tissue changes versus residual or recurrent tumor, the detection of small lesions, and possibly in the distinction of stPNET from gliomas.

Epigenetic repression of RASSF1A but not CASP8 in supratentorial PNET (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of childhood

“…For certain risk groups of the most common embryonal CNS tumor, medulloblastoma, cure rates of up to 70% have been achieved (Kortmann et al, 2000). For other types such as the ones in our study sPNET and AT/RT prognosis remains grim and metastasis at diagnosis or relapse are inevitably fatal (Packer et al, 2002;Fru¨hwald et al, 2004). While research has produced a series of potentially useful biomarkers for medulloblastoma, no such data is available for sPNET or AT/RT (Scheurlen et al, 1998;Grotzer et al, 2000).…”

Differential Expression of Somatostatin Receptors, P44/42 MAPK, and mTOR Activation in Medulloblastomas and Primitive Neuroectodermal Tumors

“…[1][2][3] Despite improvements in chemotherapy, long-term survival rates are still suboptimal, and current treatments of surgery and radiotherapy with or without chemotherapy are associated with a lower IQ, defects in memory, and hearing impairment. 4 Several studies suggest that somatostatin receptors (SSRs) or octreotide-binding sites are expressed on medulloblastomas [5][6][7][8][9] or primitive neuroectodermal tumors (PNETs) [10][11][12] and might be targeted by somatostatin ligands, such as octreotide, as a novel chemotherapy. 10,[13][14][15][16] SSR2A has been found to be overexpressed in primary and recurrent medulloblastomas.…”

Effect of Somatostatin Analogue Octreotide in Medulloblastoma in Xenograft and Cell Culture Study

“…Most cases of medulloblastoma showed high-density SSTRs by Octreoscan scintigraphy [5][6][7]. Development of long-acting somatostatin analogues raised the issue of their potential antiproliferative effect in medulloblastoma.…”

“…Somatostatin receptors (SSTR) are G-protein coupled receptors, which are overexpressed in a large variety of human tumors (neuroendocrine and gastroenteropancreatic tumors, osteosarcoma, central nervous system tumors) [1][2][3][4][5]. In vivo, high expression of SSTR 2 and 5 were described in medulloblastoma, using scintigraphy (Octreoscan) by several authors [5][6][7]. Octreotide, a SSTR agonist has antineoplastic effect, which is exerted in a direct, receptor-mediated way, leading to inhibition of cell proliferation or stimulation of apoptosis.…”