Sestamibi accumulation in human nasopharyngeal carcinoma cell lines in vitro.
Sestamibi imaging is used to assess the staging of nasopharyngeal carcinoma (NPC), and to monitor response to therapy. Sestamibi was added to single-cell suspensions of the NPC cell lines CNE-1 and CNE-2Z, and aliquots were removed over 60 min and centrifuged to determine cell-associated radioactivity. Sestamibi accumulation reached similar plateau values in both cell lines within 30 min of addition. Saturating concentrations of P-glycoprotein (Pgp) modulators increased accumulation by 1.4-1.7 fold over controls. Hyperpolarization of the mitochondrial membrane with nigericin increased accumulation by 2.6-3.4 fold. In contrast, depolarization of the plasma membrane with isotonic high potassium buffer reduced accumulation to 70-75% of control values, and additional depolarization of the mitochondrial membrane with valinomycin further reduced accumulation to 21-29% of control levels. These results indicate that both cell lines contain a modest level of Pgp activity and that both are capable of further polarization of the mitochondria. This suggests that mitochondrial hyperpolarization is not the complete explanation for high accumulation of sestamibi in NPC.
Ballinger
J R
JR
Division of Experimental Therapeutics, Ontario Cancer Institute, Toronto, Canada. jrballinger@hotmail.com
Li
J H
JH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D009550:Nigericin / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured; D014634:Valinomycin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins; D019275:Radiopharmaceuticals; D014634:Valinomycin; D016572:Cyclosporine; D017256:Technetium Tc 99m Sestamibi; D014700:Verapamil; C070272:valspodar; D009550:Nigericin; D011188:Potassium