Abstract | 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.
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Authors | Aida Kiviniemi, Maria Gardberg, Anu Autio, Xiang-Guo Li, Vanina D Heuser, Heidi Liljenbäck, Meeri Käkelä, Henri Sipilä, Jere Kurkipuro, Seppo Ylä-Herttuala, Juhani Knuuti, Heikki Minn, Anne Roivainen |
Journal | Acta oncologica (Stockholm, Sweden)
(Acta Oncol)
Vol. 53
Issue 8
Pg. 1125-34
(Aug 2014)
ISSN: 1651-226X [Electronic] England |
PMID | 24957558
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 68Ga-octreotide, DOTA(0)-Tyr(3)-
- Neoplasm Proteins
- Organometallic Compounds
- Radiopharmaceuticals
- Receptors, Somatostatin
- Fluorodeoxyglucose F18
- somatostatin receptor 2
- Octreotide
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Topics |
- Animals
- Autoradiography
- Brain
(diagnostic imaging, metabolism)
- Cell Line, Tumor
- Fluorodeoxyglucose F18
(pharmacokinetics)
- Glioma
(diagnostic imaging, metabolism)
- Male
- Mice
- Mice, Nude
- Muscle, Skeletal
(diagnostic imaging, metabolism)
- Neoplasm Proteins
(metabolism)
- Neoplasm Transplantation
(methods)
- Octreotide
(analogs & derivatives, pharmacokinetics)
- Organometallic Compounds
(pharmacokinetics)
- Positron-Emission Tomography
(methods)
- Radiopharmaceuticals
(pharmacokinetics)
- Rats
- Receptors, Somatostatin
(metabolism)
- Tomography, X-Ray Computed
(methods)
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