Old tracer for new purpose: Tc-99m-2-methoxyisobutylisonitril (Tc-99m-MIBI) for imaging nephrotoxicity

Objectives Tc-99m-MIBI is a P-glycoprotein (P-gp) substrate used for in vivo imaging of P-gp-related multidrug resistance. P-gp, an ATP-binding cassette (ABC) transporter protein, promotes the cellular efflux of cyclosporine, tacrolimus and other potentially nephrotoxic drugs. The only known mechanism of Tc-99m-MIBI elimination from renal tubular cells involves ABC transporter proteins, so Tc-99m-MIBI kinetics may indicate renal P-gp status. Some patients constitutionally express low levels of P-gp, encoded by the mdr1 gene, and may require lower doses of immuno-suppressants. The study aims were to image P-gp expression and also demonstrate that differential renal function (DRF), based on Tc-99m-MIBI, is similar to, and could replace, Tc-99m-MAG3 DRF.

Methods Thirty healthy kidney transplant donors were dynamically imaged for 20 min after injection of 400 MBq Tc-99m-MIBI. Static 5-min images were acquired at 30 and 120 min. Bland-Altman analysis was used to assess agreement between DRF based on Tc-99m-MIBI and Tc-99m-MAG3. The rate constants (k) of Tc-99m-MIBI elimination from kidney, liver, spleen and myocardium were calculated from count rates recorded at 30 and 120 min.

Results Tc-99m-MIBI and Tc-99m-MAG3 showed different patterns of renal handling but good agreement with respect to DRF. k showed no difference between liver (0.0048 [SD 0.0011] min-1) and spleen (0.00414 [0.000829] min-1; p=0.096) but was lower in the kidney (0.00225 [0.000835] min-1; p<0.001) and myocardium (0.00094 [0.000546] min-1; p<0.001). There were significant correlations between k values of all 4 tissues (R²=0.27-0.36).

Conclusions DRF can be accurately measured with Tc-99m-MIBI. The tissue elimination rates of Tc-99m-MIBI give measures of constitutional P-gp expression. All 4 organs have some level of P-gp expression, the myocardium the lowest. Tc-99m-MIBI may provide useful information regarding dose selection of nephrotoxic drugs that are P-gp substrates