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a Departments of Surgery, b Radiation Physics, and c Pathology at the Lundberg Laboratory for Cancer Research, Göteborg University, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden
Key Words: malignant pheochromocytoma • VMAT • SSTR • radionuclide therapy
Address for correspondence: Lars Kölby, M.D., Ph.D., Lundberg Laboratory for Cancer Research, Institute for Surgical Sciences, Department of Surgery, Göteborg University, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. Voice: 46-31-342-1000; fax: 46-31-41-7364. e-mail: lars.kolby{at}surgery.gu.se
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
 -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 -actin). The two patients with high VMAT expression and high 123I-MIBG uptake were treated with 131I-MIBG (2–3 x 8 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 -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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