18FDG a PET tumor diagnostic tracer is not a substrate of the ABC transporter P-glycoprotein

Krasznai, Zoltán; Trencsényi, György; Mikecz, Pál; Nizsalóczki, Enikő; Szalóki, Gábor; Szabó, Judit P.; Balkay, László; Márián, Teréz; Goda, Katalin

doi:10.1016/j.ejps.2014.08.002

Cited by 8 publications

(10 citation statements)

References 36 publications

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“…Altogether, these results confirm that 18 F-FDG is not transported by P-gp (25). Phosphorylation of 18 F-FDG by HK, as well as P-gp-mediated transport, may competitively modulate D-glucose and intracellular ATP concentration.…”

Section: Discussionsupporting

confidence: 73%

“…1). This time-dependent shift was also found in cancer cells (17,25). Interestingly, CsA was previously shown to abolish the difference in 18 F-FDG uptake between MDRpositive and MDR-negative cell lines (23).…”

Section: Discussionsupporting

confidence: 64%

“…Therefore, it was hypothesized that 18 F-FDG may be a substrate of P-gp (15,22). Conversely, it was also reported an enhanced 18 F-FDG uptake in various P-gpexpressing cancer cells compared to P-gp negative in vitro (23)(24)(25). No explanation was given so far for this discrepancy.…”

mentioning

confidence: 73%

“…First, it may be hypothesized that chemotherapeutic agents used for the selection of MDR clones may differentially affect glucose metabolism and affect 18 F-FDG uptake. In addition to the variety of cell lines and culture condition (25), we show that these controversies may result from different incubation duration used in the different studies that ranged from 10 to 120 min. Our results show that, in the absence of D-glucose, P-gp inhibition using valspodar, a CsA derivative, enhanced 18 F-FDG uptake after 120-min incubation, while it was reduced at earlier incubation times (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…It was recently shown that high concentration FDG does not impact ATP hydrolysis in P-gp-overexpressing cells (25). However, inconsistencies for P-gp substrates to impact the Pgp ATPase activity have been reported, and ATPase assay appeared insufficient to conclude to a lack of P-gp mediated transport (44).…”

Section: Discussionmentioning

confidence: 99%

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Influence of P-Glycoprotein Inhibition or Deficiency at the Blood–Brain Barrier on 18F-2-Fluoro-2-Deoxy-d-glucose (18F-FDG) Brain Kinetics

Tournier

Saba

Goutal

et al. 2015

AAPS J

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ABSTRACT. The fluorinated D-glucose analog 18 F-2-fluoro-2-deoxy-D-glucose ( 18 F-FDG) is the most prevalent radiopharmaceutical for positron emission tomography (PET) imaging. P-Glycoprotein's (P-gp, MDR1, and ABCB1) function in various cancer cell lines and tumors was shown to impact 18 F-FDG incorporation, suggesting that P-gp function at the blood-brain barrier may also modulate 18 F-FDG brain kinetics. We tested the influence of P-gp inhibition using the cyclosporine analog valspodar (PSC833; 5 μM) on the uptake of PET analysis revealed that P-gp inhibition had no significant impact on estimated brain kinetics parameters K 1 , k 2 , k 3 , V T , and CMR Glc . The lack of P-gp effect on in vivo 18 F-FDG brain distribution was confirmed in P-gp/Bcrp-deficient mice. P-gp inhibition indirectly modulates 18 F-FDG uptake into P-gp-overexpressing cells, possibly through differences in the energetic cell level state. 18F-FDG is not a P-gp substrate at the BBB and 18 F-FDG brain kinetics as well as estimated brain glucose metabolism are influenced by neither P-gp inhibition nor P-gp/Bcrp deficiencies in baboon and mice, respectively.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionsupporting

confidence: 64%

mentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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