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.
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.
Authors: T R DeGrado; R E Coleman; S Wang; S W Baldwin; M D Orr; C N Robertson; T J Polascik; D T Price Journal: Cancer Res Date: 2001-01-01 Impact factor: 12.701
Authors: M D Cordobes; A Starzec; L Delmon-Moingeon; C Blanchot; J C Kouyoumdjian; G Prévost; M Caglar; J L Moretti Journal: J Nucl Med Date: 1996-02 Impact factor: 10.057
Authors: Ludwig Rinnab; Felix M Mottaghy; Norbert M Blumstein; Sven N Reske; Richard E Hautmann; Kathrin Hohl; Peter Möller; Thomas Wiegel; Rainer Kuefer; Juergen E Gschwend Journal: BJU Int Date: 2007-10 Impact factor: 5.588
Authors: Clovis Orlando da Fonseca; Himanshu Khandelia; Marcela D'Alincourt Salazar; Axel H Schönthal; Osório C Meireles; Thereza Quirico-Santos Journal: Surg Neurol Int Date: 2016-01-05
Authors: Joo Ern Ang; Rupinder Pandher; Joo Chew Ang; Yasmin J Asad; Alan T Henley; Melanie Valenti; Gary Box; Alexis de Haven Brandon; Richard D Baird; Lori Friedman; Mika Derynck; Bart Vanhaesebroeck; Suzanne A Eccles; Stan B Kaye; Paul Workman; Johann S de Bono; Florence I Raynaud Journal: Mol Cancer Ther Date: 2016-04-05 Impact factor: 6.261
Authors: Elke Hattingen; Oliver Bähr; Johannes Rieger; Stella Blasel; Joachim Steinbach; Ulrich Pilatus Journal: PLoS One Date: 2013-03-08 Impact factor: 3.240