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Evaluation of [18F]F-DPA as a target for TSPO in head and neck cancer under normal conditions and after radiotherapy.
Tuominen, Sanni; Keller, Thomas; Petruk, Nataliia; López-Picón, Francisco; Eichin, Dominik; Löyttyniemi, Eliisa; Verhassel, Alejandra; Rajander, Johan; Sandholm, Jouko; Tuomela, Johanna; Grönroos, Tove J.
Afiliação
  • Tuominen S; Preclinical Imaging Laboratory, Turku PET Centre, University of Turku, Tykistökatu 6A, FI-20520, Turku, Finland.
  • Keller T; Institute of Biomedicine and FICAN West Cancer Research Laboratory, University of Turku, Kiinamyllynkatu 10, FI-20520, Turku, Finland.
  • Petruk N; MediCity Research Laboratory, University of Turku, Tykistökatu 6A, FI-20520, Turku, Finland.
  • López-Picón F; Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland.
  • Eichin D; Institute of Biomedicine and FICAN West Cancer Research Laboratory, University of Turku, Kiinamyllynkatu 10, FI-20520, Turku, Finland.
  • Löyttyniemi E; Preclinical Imaging Laboratory, Turku PET Centre, University of Turku, Tykistökatu 6A, FI-20520, Turku, Finland.
  • Verhassel A; MediCity Research Laboratory, University of Turku, Tykistökatu 6A, FI-20520, Turku, Finland.
  • Rajander J; MediCity Research Laboratory, University of Turku, Tykistökatu 6A, FI-20520, Turku, Finland.
  • Sandholm J; Department of Biostatistics, University of Turku, Kiinamyllynkatu 10, FI-20520, Turku, Finland.
  • Tuomela J; Institute of Biomedicine and FICAN West Cancer Research Laboratory, University of Turku, Kiinamyllynkatu 10, FI-20520, Turku, Finland.
  • Grönroos TJ; Accelerator Laboratory, Turku PET Centre, Åbo Akademi University, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland.
Eur J Nucl Med Mol Imaging ; 48(5): 1312-1326, 2021 05.
Article em En | MEDLINE | ID: mdl-33340054
ABSTRACT

BACKGROUND:

Many malignant tumours have increased TSPO expression, which has been related to a poor prognosis. TSPO-PET tracers have not comprehensively been evaluated in peripherally located tumours. This study aimed to evaluate whether N,N-diethyl-2-(2-(4-([18F]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide ([18F]F-DPA) can reflect radiotherapy (RT)-induced changes in TSPO activity in head and neck squamous cell carcinoma (HNSCC).

METHODS:

RT was used to induce inflammatory responses in HNSCC xenografts and cells. [18F]F-DPA uptake was measured in vivo in non-irradiated and irradiated tumours, followed by ex vivo biodistribution, autoradiography, and radiometabolite analysis. In vitro studies were performed in parental and TSPO-silenced (TSPO siRNA) cells. TSPO protein and mRNA expression, as well as tumour-associated macrophages (TAMs), were also assessed.

RESULTS:

In vivo imaging and ex vivo measurement revealed significantly higher [18F]F-DPA uptake in irradiated, compared to non-irradiated tumours. In vitro labelling studies with cells confirmed this finding, whereas no effect of RT on [18F]F-DPA uptake was detected in TSPO siRNA cells. Radiometabolite analysis showed that the amount of unchanged [18F]F-DPA in tumours was 95%, also after irradiation. PK11195 pre-treatment reduced the tumour-to-blood ratio of [18F]F-DPA by 73% in xenografts and by 88% in cells. TSPO protein and mRNA levels increased after RT, but were highly variable. The proportion of M1/M2 TAMs decreased after RT, whereas the proportion of monocytes and migratory monocytes/macrophages increased.

CONCLUSIONS:

[18F]F-DPA can detect changes in TSPO expression levels after RT in HNSCC, which does not seem to reflect inflammation. Further studies are however needed to clarify the physiological mechanisms regulated by TSPO after RT.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Radioisótopos de Flúor / Neoplasias de Cabeça e Pescoço Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Eur J Nucl Med Mol Imaging Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Radioisótopos de Flúor / Neoplasias de Cabeça e Pescoço Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Eur J Nucl Med Mol Imaging Ano de publicação: 2021 Tipo de documento: Article