IMAGING OF SOMATOSTATIN RECEPTORS BY INDIUM-111-PENTETREOTIDE CORRELATES WITH QUANTITATIVE-DETERMINATION OF SOMATOSTATIN RECEPTOR-TYPE-2 GENE-EXPRESSION IN NEUROBLASTOMA TUMORS

We reported previously that the relative level of gene expression for sst2, a subtype of somatostatin receptors, was positively related to p atient outcome in the childhood tumor neuroblastoma (NB), Because sst2 binds with high-affinity octreotide and its scintigraphic derivative, In-111-pentetreotide, we tested the hypothesis of whether NB tumor im aging with In-111-pentetreotide gives similar information to ex vivo m easurement of sst2 expression, We, therefore, studied simultaneously n ine NB tumors with In-111-pentetreotide single photon emission compute d tomography and competitive reverse transcription-PCR for sst2, along with other prognostic markers. To quantitate the relative abundance o f In-111-pentetreotide binding to NB tumors, we developed a simple sem iquantitative method, based on the mathematical analysis of In-111-pen tetreotide association to cancer cell receptors at different time poin ts (4 and 24 h), We indeed found that the ratio between the activity i n a manually extracted region of interest from pathological (ROIT) and background (ROINT) area was increasing between early and late acquisi tion only in affected tissues, The rate of this pathological increase was quite different among patients and significantly (P < 0.01) relate d to the abundance of sst2 gene expression, as measured by competitive reverse transcription-PCR on ex vivo tumor samples, Because we demons trated that in 26 NB patients the density of sst2 is strongly related to survival (P < 0.0005) and apparently independent from N-myc oncogen e amplification (P < 0.05), we propose that NB tumor imaging with In-1 11-pentetreotide may have not only a diagnostic but also a prognostic value.