Elsevier

Journal of Pediatric Surgery

Volume 30, Issue 11, November 1995, Pages 1580-1589
Journal of Pediatric Surgery

Intraoperative detection and resection of occult neuroblastoma: A technique exploiting somatostatin receptor expression,☆☆

https://doi.org/10.1016/0022-3468(95)90161-2Get rights and content

Abstract

Tumor cell expression of specific high-affinity somatostatin receptors has been associated with a favorable prognosis in children with neuroblastoma. The purpose of this study was (1) to document intraoperatively the in vivo binding of the somatostatin analogue 125I-tyr3-octreotide to highaffinity somatostatin receptors expressed on human neuroblastoma, using a hand-held gamma detector; (2) to determine whether gamma-probe detection of radioligand binding to tumor receptors could identify occult malignancy; and (3) to determine the safety and biodistribution of 125I-tyr3-octreotide in children. Six children with stage III or IV neuroblastoma received an intravenous injection of 125I-tyr3-octreotide and underwent operative exploration using gamma-probe detection of radioligand binding to tumor somatostatin receptors. Tissue that demonstrated in vivo binding of 125I-tyr3-octreotide, or that was suspicious for tumor, was extirpated and analyzed by histopathology, immunohistochemistry, and microautoradiography. The biodistribution of 125I-tyr3-octreotide was recorded intraoperatively over time. Tumor tissue from each child also was assayed in vitro for somatostatin receptor expression by competitive binding studies using 125I-tyr3-octreotide. In vivo binding of 125I-tyr3-octreotide to malignant tissue was documented in the five children with a known tumor burden. Seventeen sites of radioreceptor binding were amenable to resection. Histopathological analysis confirmed neuroblastoma in 15 of these specimens. Four of the 15 proven tumor foci were occult malignancies. Every site of histologically proven neuroblastoma demonstrated in vivo binding of 125I-tyr3-octreotide. Five of seven sites histologically negative for neuroblastoma also were negative for in vivo radioreceptor binding. Microautoradiography confirmed in vivo binding of 125I-tyr3-octreotide to tumor cells. Uptake of 125I-tyr3-octreotide in abdominal organs occurred within 15 minutes of injection, was highest in the liver and gallbladder, and decreased over 24 hours. The conclusions were as follows. (1) 125I-tyr3-octreotide binds, in vivo, to somatostatin receptors on neuroblastoma, with 100% sensitivity and 71% specificity. (2) Occult neuroblastoma is found through gammaproble detection of radioligand binding to receptors. (3) The biodistribution of 125I-tyr3-octreotide reflects the hepatobiliary clearance of this radionuclide. (4) Radioreceptor-guided surgery may safely provide more complete operative staging and cytoreduction of neuroblastoma.

References (53)

  • F Chen et al.

    Mechanism of action of long-acting analogs of somatostatin

    Regul Pept

    (1993)
  • JC Reubi

    Novel selective radioligand for one population of rat cortexsomatostain receptors

    Life Sci

    (1985)
  • GA McPherson

    Analysis of radioligand binding experiments: A collection of computer programs for the IBM PC

    J Pharmacol Method

    (1985)
  • PJ Munson et al.

    LIGAND: A versatile computerized approach for the characterization of ligand binding systems

    Anal Biochem

    (1980)
  • JA O'Neill et al.

    The role of surgery in localized neuroblastoma

    J Pediatr Surg

    (1985)
  • M Matsumura et al.

    An evaluation of the role of surgery in metastatic neuroblastoma

    J Pediatr Surg

    (1988)
  • A Sitarz et al.

    An evaluation of the role of surgery in disseminated neuroblastoma: A report from the Children's Cancer Study Group

    J Pediatr Surg

    (1983)
  • DA Martinez et al.

    Resection of the primary tumor is appropriate for children with stage IV-S neuroblastoma: An analysis of 37 patients

    J Pediatr Surg

    (1992)
  • GM Haase et al.

    Surgical management and outcome of locoregional neuroblastoma: Comparison of the Childrens Cancer Group and the International Staging Systems

    J Pediatr Surg

    (1995)
  • K Ikeda et al.

    Improved survival rates in children over 1 year of age with stage III or IV neuroblastoma following an intensive chemotherapeutic regimen

    J Pediatr Surg

    (1989)
  • MP LaQuaglia et al.

    Stage 4 neuroblastoma diagnosed at more than 1 year of age: Gross total resection and clinical outcome

    J Pediatr Surg

    (1994)
  • H Ikeda et al.

    Sites of relapse in patients with neuroblastoma following bone marrow transplantation in relation of preparatory “debulking” treatments

    J Pediatr Surg

    (1992)
  • SJ Qualman et al.

    Neuroblastoma: Correlation of tumor neuropeptide contents with known prognostic factors

    Cancer

    (1992)
  • MS O'Dorisio et al.

    Characterization of somatostatin receptors on human neuroblastoma tumors

    Cell Growth Differentiation

    (1994)
  • M Maggi et al.

    Identification, characterization, and biological activity of somatostatin receptors in human neuroblastoma cell lines

    Cancer Res

    (1994)
  • MMT O'Hare et al.

    Expression and precursor processing of neuropeptide Y in human pheochromocytoma and neuroblastoma tumors

    Cancer Res

    (1989)
  • Cited by (20)

    • Radioguided surgery in neuroendocrine tumors. A review of the literature

      2014, Revista Espanola de Medicina Nuclear e Imagen Molecular
    View all citing articles on Scopus

    Presented in part at the 46th Annual Symposium of the Society of Surgical Oncology, Los Angeles, California, March 20, 1993.

    ☆☆

    Supported by grants from NCI RO1CA41997 (MSO), Children's Hospital Research Foundation (MSO), NIH MO1 RR00034 (TMO), and Ohio Edison Biotechnology (MSO). Deborah A. Martinez was supported by an ACS Fellowship.

    View full text