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Can quantification of VMAT and SSTR expression be helpful for planning radionuclide therapy of malignant pheochromocytomas?

Journal article
Authors Lars Kölby
Peter Bernhardt
Viktor Johanson
Bo Wängberg
Andreas Muth
Svante Jansson
Eva Forssell-Aronsson
Ola Nilsson
Håkan Ahlman
Published in Annals of the New York Academy of Sciences
Volume 1073
Pages 491-7
ISSN 0077-8923
Publication year 2006
Published at Institute of Clinical Sciences, Department of Radiation Physics
Institute of Clinical Sciences, Department of Surgery
Institute of Clinical Sciences, Department of Plastic Surgery
Pages 491-7
Language en
Keywords 3-Iodobenzylguanidine, therapeutic use, Cell Line, Tumor, Humans, Iodine Radioisotopes, therapeutic use, Receptors, Somatostatin, metabolism, Vesicular Monoamine Transport Proteins, metabolism
Subject categories Cancer and Oncology, Surgery


Tumor-specific uptake of the radio-iodinated norepinephrine analogue meta-iodobenzylguanidine (MIBG) or uptake of radiolabeled somatostatin analogues via somatostatin receptors (SSTRs) are possibilities to diagnose and treat malignant pheochromocytomas/paragangliomas (PCs/PGs). The aims of this study were to investigate the quantitative expression of vesicular monoamine transporters (VMAT 1, 2) and all five SSTRs in malignant pheochromocytoma/paraganglioma (PC/PG) to evaluate the possibilities for tumor-specific radionuclide therapy. High scintigraphic 123I-MIBG uptake was found in two malignant PGs with high VMAT expression (500-730 copies of VMAT 1, 1,500-1,700 copies of VMAT 2 per 1,000 beta-actin), while no 123I-MIBG uptake was found in the malignant PG with low VMAT expression (330 copies of VMAT 1, 350 copies of VMAT 2 per 1,000 beta-actin). The two patients with high VMAT expression and high 123I-MIBG uptake were treated with 131I-MIBG (2-3x8 GBq). In vitro, the VMAT antagonist, reserpine, and the membrane pump inhibitor, clomipramine, inhibited the uptake of 123I-MIBG into tumor cells equally well (48% and 53% reduction respectively, P<0.001). SSTR2 was the most abundant receptor subtype, but in the two malignant PGs its expression was only 110-260 copies/1,000 beta-actin. The transporters at the cell membrane and in the vesicular membrane both appear to be of importance for the uptake of 123I-MIBG into malignant PC/PG. Quantitative determination of VMAT expression may be helpful in selecting patients suitable for radionuclide therapy with 131I-MIBG. The present data indicate that SSTR-mediated radionuclide therapy will not be effective treatment of malignant PC/PG.

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