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Published on: March 6, 2012
Feasibility of experimental BT4C glioma models for somatostatin receptor 2-targeted therapies
Aida Kiviniemi1, Maria Gardberg, Anu Autio
1Turku PET Centre, Turku University Hospital and University of Turku , Turku , Finland.
Unlabelled:
Somatostatin receptor subtype 2 (sstr2) is regarded as a potential target in malignant gliomas for new therapeutic approaches. Therefore, visualizing and quantifying tumor sstr2 expression in vivo would be highly relevant for the future development of sstr2-targeted therapies. The purpose of this study was to evaluate sstr2 status in experimental BT4C malignant gliomas.
Methods:
Rat BT4C malignant glioma cells were injected into BDIX rat brain or subcutaneously into nude mice. Tumor uptake of [(68)Ga]DOTA-(Tyr(3))-Octreotide ([(68)Ga]DOTATOC), a somatostatin analog binding to sstr2, was studied by positron emission tomography/computed tomography (PET/CT). Additionally, subcutaneous tumor-bearing mice underwent PET imaging with 5-deoxy-5-[(18)F]fluororibose-NOC ([(18)F]FDR-NOC), a novel glycosylated peptide tracer also targeting sstr2. Ex vivo tissue radioactivity measurements, autoradiography and immunohistochemistry were performed to study sstr2 expression.
Results:
Increased tumor uptake of [(68)Ga]DOTATOC was detected at autoradiography with mean tumor-to-brain ratio of 68 ± 30 and tumor-to-muscle ratio of 9.2 ± 3.8 for rat glioma. High tumor-to-muscle ratios were also observed in subcutaneous tumor-bearing mice after injection with [(68)Ga]DOTATOC and [(18)F]FDR-NOC with both autoradiography (6.7 ± 1.5 and 4.3 ± 0.8, respectively) and tissue radioactivity measurements (6.5 ± 0.8 and 4.8 ± 0.6, respectively). Furthermore, sstr2 immunohistochemistry showed positive staining in both tumor models. However, surprisingly low tumor signal compromised PET imaging. Mean SUVmax for rat gliomas was 0.64 ± 0.28 from 30 to 60 min after [(68)Ga]DOTATOC injection. The majority of subcutaneous tumors were not visualized by [(68)Ga]DOTATOC or [(18)F]FDR-NOC PET.
Conclusions:
Experimental BT4C gliomas show high expression of sstr2. Weak signal in PET imaging, however, suggests only limited benefit of [(68)Ga]DOTATOC or [(18)F]FDR-NOC PET/CT in this tumor model for in vivo imaging of sstr2 status.
Insights
Somatostatin receptor subtype 2 (sstr2) is highly expressed in experimental BT4C gliomas. However, positron emission tomography/computed tomography (PET/CT) imaging with sstr2-targeted tracers showed weak tumor signals, limiting their use for in vivo visualization.
Area of Science:
- Neuro-oncology
- Molecular Imaging
- Radiopharmaceuticals
Background:
- Somatostatin receptor subtype 2 (sstr2) is a potential therapeutic target in malignant gliomas.
- In vivo visualization and quantification of sstr2 expression are crucial for developing targeted therapies.
Purpose of the Study:
- To evaluate the sstr2 status in experimental BT4C malignant gliomas.
- To assess the utility of PET/CT imaging for visualizing sstr2 expression in this model.
Main Methods:
- BT4C malignant glioma cells were implanted in rat brains and in mice.
- Tumor uptake of [(68)Ga]DOTATOC and [(18)F]FDR-NOC, sstr2-targeting tracers, was evaluated using PET/CT.
- Ex vivo autoradiography, tissue radioactivity measurements, and immunohistochemistry were performed.
Main Results:
- Autoradiography and immunohistochemistry confirmed high sstr2 expression in both rat and mouse glioma models.
- PET imaging demonstrated low tumor-to-background ratios, with most tumors not being visualized.
- Mean SUVmax in rat gliomas was low (0.64 ± 0.28) after [(68)Ga]DOTATOC injection.
Conclusions:
- Experimental BT4C gliomas exhibit high sstr2 expression.
- Despite high receptor expression, PET/CT imaging with [(68)Ga]DOTATOC and [(18)F]FDR-NOC yielded weak signals.
- The limited signal in PET imaging suggests restricted clinical benefit for in vivo sstr2 status assessment in this glioma model.
