title: Imaging of somatostatin receptors by indium-111-pentetreotide correlates with quantitative determination of somatostatin receptor type 2 gene expression in neuroblastoma tumors.
abstract: We reported previously that the relative level of gene expression for sst2, a subtype of somatostatin receptors, was positively related to patient outcome in the childhood tumor neuroblastoma (NB). Because sst2 binds with high-affinity octreotide and its scintigraphic derivative, 111In-pentetreotide, we tested the hypothesis of whether NB tumor imaging with 111In-pentetreotide gives similar information to ex vivo measurement of sst2 expression. We, therefore, studied simultaneously nine NB tumors with 111In-pentetreotide single photon emission computed tomography and competitive reverse transcription-PCR for sst2, along with other prognostic markers. To quantitate the relative abundance of 111In-pentetreotide binding to NB tumors, we developed a simple semiquantitative method, based on the mathematical analysis of 111In-pentetreotide association to cancer cell receptors at different time points (4 and 24 h). We indeed found that the ratio between the activity in a manually extracted region of interest from pathological (ROIT) and background (ROINT) area was increasing between early and late acquisition only in affected tissues. The rate of this pathological increase was quite different among patients and significantly (P < 0.01) related to the abundance of sst2 gene expression, as measured by competitive reverse transcription-PCR on ex vivo tumor samples. Because we demonstrated that in 26 NB patients the density of sst2 is strongly related to survival (P < 0.0005) and apparently independent from N-myc oncogene amplification (P < 0.05), we propose that NB tumor imaging with 111In-pentetreotide may have not only a diagnostic but also a prognostic value.
authors.affiliation: Nuclear Medicine, University of Florence, 50139 Florence, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Briganti
authors.forename: R
authors.initials: R
authors.lastname: Sestini
authors.forename: C
authors.initials: C
authors.lastname: Orlando
authors.forename: G
authors.initials: G
authors.lastname: Bernini
authors.forename: G
authors.initials: G
authors.lastname: La Cava
authors.forename: A
authors.initials: A
authors.lastname: Tamburini
authors.forename: C C
authors.initials: CC
authors.lastname: Raggi
authors.forename: M
authors.initials: M
authors.lastname: Serio
authors.forename: M
authors.initials: M
authors.lastname: Maggi
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D000328:Adult; D000782:Aneuploidy; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D007205:Indium Radioisotopes; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin / Q000032:analysis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D007205:Indium Radioisotopes; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2; C081788:pentetreotide