Accumulation of Sestamibi in Lymphoma Cell Lines In Vitro

Abstract

Although some authors have suggested that sestamibi imaging is useful in evaluation of patients with lymphoma, others have obtained equivocal results. This discrepancy has been further investigated in vitro using two patient-derived non-Hodgkin's lymphoma cell lines, OCI-Ly3 and OCI-Ly18.

Sestamibi (0.2 MBq/ml) was added to a suspension of OCI-Ly3 or OCI-Ly18 cells and aliquots were removed over 1 h and centrifuged to determine cell-associated radioactivity. Further experiments studied the effect of addition of a P-glycoprotein (Pgp) modulator or alteration in plasma and/or mitochondrial membrane potentials.

Accumulation of sestamibi reached plateau values within 30 min, but these values were 6-fold higher in OCI-Ly3 than in OCI-Ly18. Inhibition of Pgp function with GG918 or PSC833 did not affect OCI-Ly3 cells but increased accumulation in OCI-Ly18 cells 3-fold, indicating a moderate level of Pgp. However, both cell lines responded similarly to membrane potential alterations: hyperpolarization of the mitochondrial membrane with nigericin had little effect on accumulation; in contrast, depolarization of the plasma membrane with an isotonic high potassium buffer reduced accumulation of sestamibi to 52% of control and additional depolarization of the mitochondrial membrane with valinomycin further reduced accumulation to 12% of control levels.

These studies suggest that there can be wide differences in accumulation between cell lines, in part due to Pgp-mediated efflux, but that both of these cell lines have highly polarized mitochondria with little further capacity for hyperpolarization.

Key Words:

• Sestamibi
• human lymphoma
• lymphoma cells
• multidrug resistance