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Specific binding and uptake of 131I-MIBG and 111In-octreotide in metastatic paraganglioma--tools for choice of radionuclide therapy.

Abstract
Tumor-specific uptake of the radiolabeled nor-epinephrine analogue meta-iodobenzylguanidine via norepinephrine transporter or radiolabeled somatostatin analogues octreotide/octreotate via somatostatin receptors offers possibilities to diagnose and treat metastatic pheochromocytoma/paraganglioma. High uptake of 123I-meta-iodobenzylguanidine is dependent on high expression of vesicular monoamine transporters responsible for mediating uptake of biogenic amines into dense core granules. A patient with metastatic paraganglioma (liver and bone metastases) underwent surgical removal of the primary after injection of 131I-meta-iodobenzylguanidine and 111In-octreotide. Radioactivity was determined in biopsies from tumor and normal tissue biopsies. The tumor/blood concentration value was high: 180 for 131I-meta-iodobenzylguanidine 3 h after injection and 590 for 111In-octreotide 27 h after injection. Studies of primary tumor cell cultures demonstrated increased cell membrane binding and internalization over time for 131I-meta-iodobenzylguanidine. The vesicular monoamine transporter antagonist reserpine and the norepinephrine transporter inhibitor clomipramine reduced internalization by 90% and 70%, respectively, after 46 h of incubation. The results demonstrated increased cell membrane binding and internalization over time also for 111In-octreotide. Internalization was highest for a low concentration of 111In-octreotide. Excess of octreotide reduced internalization of 111In-octreotide with 75% after 46 h of incubation. In conclusion, uptake and tumor/blood concentration values of radiolabeled meta-iodobenzylguanidine and somatostatin analogues can be determined for metastatic pheochromocytoma/paraganglioma to evaluate the possibility to use one or both agents for therapy. For this patient, the high tumor/blood values clearly demonstrated that therapy using both radiopharmaceuticals would be most beneficial. In vitro studies verified specific cell-membrane binding and internalization in tumor cells of both radiopharmaceuticals.
AuthorsJ Spetz, J Dalmo, O Nilsson, B Wängberg, H Ahlman, E Forssell-Aronsson
JournalHormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme (Horm Metab Res) Vol. 44 Issue 5 Pg. 400-4 (May 2012) ISSN: 1439-4286 [Electronic] Germany
PMID22566195 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Copyright© Georg Thieme Verlag KG Stuttgart · New York.
Chemical References
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • indium-111-octreotide
  • 3-Iodobenzylguanidine
  • Octreotide
Topics
  • 3-Iodobenzylguanidine (pharmacokinetics, therapeutic use)
  • Adrenal Gland Neoplasms (metabolism, pathology, radiotherapy)
  • Female
  • Humans
  • Iodine Radioisotopes (pharmacokinetics, therapeutic use)
  • Middle Aged
  • Neoplasm Metastasis
  • Octreotide (analogs & derivatives, pharmacokinetics, therapeutic use)
  • Pheochromocytoma (metabolism, pathology, radiotherapy)
  • Radiopharmaceuticals (pharmacokinetics, therapeutic use)
  • Tumor Cells, Cultured

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