title: 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.
authors.affiliation: Department of Radiation Physics, Sahlgrenska Cancer Center, University of Gothenburg, Göteborg, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Spetz
authors.forename: J
authors.initials: J
authors.lastname: Dalmo
authors.forename: O
authors.initials: O
authors.lastname: Nilsson
authors.forename: B
authors.initials: B
authors.lastname: Wängberg
authors.forename: H
authors.initials: H
authors.lastname: Ahlman
authors.forename: E
authors.initials: E
authors.lastname: Forssell-Aronsson
mesh_terms: D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010673:Pheochromocytoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; C094279:indium-111-octreotide; D019797:3-Iodobenzylguanidine; D015282:Octreotide