Related Experiment Video
Updated: Jul 18, 2026
Radionuclide-fluorescence Reporter Gene Imaging to Track Tumor Progression in Rodent Tumor Models
Published on: March 13, 2018
Can quantification of VMAT and SSTR expression be helpful for planning radionuclide therapy of malignant
Lars Kölby1, Peter Bernhardt, Viktor Johanson
1Lundberg Laboratory for Cancer Research, Institute for Surgical Sciences, Department of Surgery, Göteborg University, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. lars.kolby@surgery.gu.se
Abstract:
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.
Insights
Vesicular monoamine transporter (VMAT) expression levels predict uptake of radio-iodinated meta-iodobenzylguanidine (MIBG) in malignant pheochromocytomas/paragangliomas. Quantitative VMAT assessment can guide patient selection for MIBG radionuclide therapy.
Area of Science:
- Nuclear Medicine
- Oncology
- Endocrinology
Background:
- Malignant pheochromocytomas/paragangliomas (PC/PG) pose diagnostic and therapeutic challenges.
- Radio-iodinated meta-iodobenzylguanidine (MIBG) and radiolabeled somatostatin analogues (SSTRs) are potential agents for PC/PG diagnosis and treatment.
- Understanding the expression of vesicular monoamine transporters (VMAT) and SSTRs is crucial for optimizing radionuclide therapy.
Purpose of the Study:
- To quantitatively assess the expression of VMAT 1, VMAT 2, and all five SSTR subtypes in malignant PC/PG.
- To evaluate the potential for tumor-specific radionuclide therapy based on transporter and receptor expression.
- To correlate scintigraphic 123I-MIBG uptake with VMAT expression levels in malignant PC/PG.
Main Methods:
- Quantitative analysis of VMAT 1, VMAT 2, and SSTR expression in malignant PC/PG tissues.
- Scintigraphic imaging using 123I-MIBG to assess tumor uptake.
- In vitro studies using VMAT antagonists (reserpine) and membrane pump inhibitors (clomipramine) to evaluate MIBG uptake mechanisms.
Main Results:
- High 123I-MIBG uptake correlated significantly with high VMAT expression in malignant PGs.
- Malignant PG with low VMAT expression showed no significant 123I-MIBG uptake.
- SSTR2 was the most abundant SSTR subtype, but its expression was low in malignant PC/PG, suggesting limited efficacy for SSTR-mediated therapy.
Conclusions:
- Quantitative determination of VMAT expression is a valuable tool for selecting patients eligible for 131I-MIBG radionuclide therapy.
- Both cell membrane and vesicular membrane transporters are important for 123I-MIBG uptake in malignant PC/PG.
- SSTR-mediated radionuclide therapy is unlikely to be effective for malignant PC/PG due to low SSTR expression.
