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

Lars Kölby, Peter Bernhardt, Viktor Johanson, Bo Wängberg, Andreas Muth, Svante Jansson, Eva Forssell-Aronsson, Ola Nilsson, Håkan Ahlman
Annals of the New York Academy of Sciences 2006, 1073: 491-7
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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