TSPO PET for glioma imaging using the novel ligand 18F-GE-180: first results in patients with glioblastoma

Albert, Nathalie L.; Unterrainer, Marcus; Fleischmann, Daniel; Lindner, Simon; Vettermann, Franziska; Brunegraf, Anika; Vomacka, Lena; Brendel, Matthias; Wenter, Vera; Wetzel, Christian H.; Rupprecht, Rainer; Tonn, Jörg C.; Belka, Claus; Bartenstein, Peter; Niyazi, Maximilian

doi:10.1007/s00259-017-3799-9

Cited by 96 publications

(86 citation statements)

References 46 publications

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“…Consistent with previous studies [41], which demonstrated the presence of TSPO protein in the prostate [23,26,42,43,44], brain [38,44,45,46,47,48], stomach [23,44], colon [23,29,44,49], liver [23,44,50,51,52], lung [23,44,53], breast [23,54], and kidney [21,55,56]. Tspo mRNA transcription was observed to occur in most epithelial cells of the prostate, glia, and neurons of the brain, parietal cells, chief cells, and in the surface and neck mucous cells of the gastric glands of the stomach, hepatocytes, endothelial cells of the sinusoids, and Kupffer cells of the liver, most of the epithelial cells, goblet cells, and absorptive cells of the colon, most of the epithelial cells and macrophages of the lung, most of the epithelial cells of breast, most of the epithelial cells of the PCT, vasa recta, thin ascending and descending limbs, thick ascending limb, DCT, collecting tubule, collecting duct, and in the endothelial cells of the glomerulus of the kidney.…”

Section: Discussionsupporting

confidence: 92%

“…This would indicate a limited sensitivity in the use of Tspo mRNA as a biomarker for these cancers. However, radiolabelled TSPO ligands have shown high sensitivity for detecting the levels of TSPO protein in prostate [42] and brain cancer [45]. Another study indicated that TSPO is a poor biomarker for the diagnosis and prognosis of liver cancer, despite its upregulation in hepatocellular carcinomas [50].…”

Section: Discussionmentioning

confidence: 99%

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Translocator Protein (TSPO) as a Potential Biomarker in Human Cancers

Bhoola

Mbita

Hull

et al. 2018

IJMS

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TSPO is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed that the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer, and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney, and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of Tspo mRNA is not necessarily a good diagnostic biomarker in most cancers with changes not being large enough to be significantly different when detected by in situ hybridisation.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Translocator Protein (TSPO) as a Potential Biomarker in Human Cancers

Bhoola

Mbita

Hull

et al. 2018

IJMS

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“…The patient was scanned at the Department of Nuclear Medicine, University hospital of Munich, by an established TSPO‐PET protocol (Albert et al , ). In brief, PET was acquired with a PET/CT scanner (Biograph 64, Siemens) 60–80 min after intravenous injection of 187 MBq of 18 F‐GE180.…”

Section: Methodsmentioning

confidence: 99%

Opposite microglial activation stages upon loss of PGRN or TREM 2 result in reduced cerebral glucose metabolism

et al. 2019

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Microglia adopt numerous fates with homeostatic microglia ( HM ) and a microglial neurodegenerative phenotype ( MG nD) representing two opposite ends. A number of variants in genes selectively expressed in microglia are associated with an increased risk for neurodegenerative diseases such as Alzheimer's disease ( AD ) and frontotemporal lobar degeneration ( FTLD ). Among these genes are progranulin ( GRN ) and the triggering receptor expressed on myeloid cells 2 ( TREM 2 ). Both cause neurodegeneration by mechanisms involving loss of function. We have now isolated microglia from Grn −/− mice and compared their transcriptomes to those of Trem2 −/− mice . Surprisingly, while loss of Trem2 enhances the expression of genes associated with a homeostatic state, microglia derived from Grn −/− mice showed a reciprocal activation of the MG nD molecular signature and suppression of gene characteristic for HM . The opposite mRNA expression profiles are associated with divergent functional phenotypes. Although loss of TREM 2 and progranulin resulted in opposite activation states and functional phenotypes of microglia, FDG (fluoro‐2‐deoxy‐ d ‐glucose)‐μ PET of brain revealed reduced glucose metabolism in both conditions, suggesting that opposite microglial phenotypes result in similar wide spread brain dysfunction.

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“…The 18 kDa translocator protein (TSPO), also known as a peripheral‐type benzodiazepine receptor, is mainly expressed in an outer mitochondrial membrane, and its expression is upregulated by specific types of neoplastic cells such as gliomas, activated microglia, and reactive astrocytes associated with neuroinflammation. Additionally, it has been suggested that TSPO could be a hallmark of cellular‐differentiation in NS/PCs analogous to Nestin, which is widely known as an NS/PC marker .…”

Section: Introductionmentioning

confidence: 99%

In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation

Tanimoto

Yamasaki

Nagoshi

et al. 2020

Stem Cells Translational Medicine

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Transplantation of human‐induced pluripotent stem cell‐derived neural stem/progenitor cells (hiPSC‐NS/PCs) is a promising treatment for a variety of neuropathological conditions. Although previous reports have indicated the effectiveness of hiPSC‐NS/PCs transplantation into the injured spinal cord of rodents and nonhuman primates, long‐term observation of hiPSC‐NS/PCs post‐transplantation suggested some “unsafe” differentiation‐resistant properties, resulting in disordered overgrowth. These findings suggest that, even if “safe” NS/PCs are transplanted into the human central nervous system (CNS), the dynamics of cellular differentiation of stem cells should be noninvasively tracked to ensure safety. Positron emission tomography (PET) provides molecular‐functional information and helps to detect specific disease conditions. The current study was conducted to visualize Nestin (an NS/PC marker)‐positive undifferentiated neural cells in the CNS of immune‐deficient (nonobese diabetic‐severe combined immune‐deficient) mice after hiPSC‐NS/PCs transplantation with PET, using 18 kDa translocator protein (TSPO) ligands as labels. TSPO was recently found to be expressed in rodent NS/PCs, and its expression decreased with the progression of neuronal differentiation. We hypothesized that TSPO would also be present in hiPSC‐NS/PCs and expressed strongly in residual immature neural cells after transplantation. The results showed high levels of TSPO expression in immature hiPSC‐NS/PCs‐derived cells, and decreased TSPO expression as neural differentiation progressed in vitro. Furthermore, PET with [18F] FEDAC (a TSPO radioligand) was able to visualize the remnant undifferentiated hiPSC‐NS/PCs‐derived cells consisting of TSPO and Nestin+ cells in vivo. These findings suggest that PET with [18F] FEDAC could play a key role in the safe clinical application of CNS repair in regenerative medicine.

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TSPO PET for glioma imaging using the novel ligand 18F-GE-180: first results in patients with glioblastoma

Cited by 96 publications

References 46 publications

Translocator Protein (TSPO) as a Potential Biomarker in Human Cancers

Translocator Protein (TSPO) as a Potential Biomarker in Human Cancers

Opposite microglial activation stages upon loss of PGRN or TREM 2 result in reduced cerebral glucose metabolism

In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation

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