Details

Autor(en) / Beteiligte

• Vanpouille, Claire
• Le Jeune, Nathalie
• Kryza, David
• Clotagatide, Anthony
• Janier, Marc
• Dubois, Francis
• Perek, Nathalie

Titel

Influence of multidrug resistance on 18F-FCH cellular uptake in a glioblastoma model

Ist Teil von

• European journal of nuclear medicine and molecular imaging, 2009-08, Vol.36 (8), p.1256-1264

Ort / Verlag

Berlin/Heidelberg: Springer-Verlag

Erscheinungsjahr

2009

Link zum Volltext

Quelle

SpringerNature Journals

Beschreibungen/Notizen

• Purpose Multidrug resistance, aggressiveness and accelerated choline metabolism are hallmarks of malignancy and have motivated the development of new PET tracers like 18 F-FCH, an analogue of choline. Our aim was to study the relationship of multidrug resistance of cultured glioma cell lines and 18 F-FCH tracer uptake. Methods We used an in vitro multidrug-resistant (MDR) glioma model composed of sensitive parental U87MG and derived resistant cells U87MG-CIS and U87MG-DOX. Aggressiveness, choline metabolism and transport were studied, particularly the expression of choline kinase (CK) and high-affinity choline transporter (CHT1). FCH transport studies were assessed in our glioblastoma model. Results As expected, the resistant cell lines express P-glycoprotein (Pgp), multidrug resistance-associated protein isoform 1 (MRP1) and elevated glutathione (GSH) content and are also more mobile and more invasive than the sensitive U87MG cells. Our results show an overexpression of CK and CHT1 in the resistant cell lines compared to the sensitive cell lines. We found an increased uptake of FCH (in % of uptake per 200,000 cells) in the resistant cells compared to the sensitive ones (U87MG: 0.89 ± 0.14; U87MG-CIS: 1.27 ± 0.18; U87MG-DOX: 1.33 ± 0.13) in line with accelerated choline metabolism and aggressive phenotype. Conclusions FCH uptake is not influenced by the two ATP-dependant efflux pumps: Pgp and MRP1. FCH would be an interesting probe for glioma imaging which would not be effluxed from the resistant cells by the classic MDR ABC transporters. Our results clearly show that FCH uptake reflects accelerated choline metabolism and is related to tumour aggressiveness and drug resistance.