Renal Scintigraphy Using Tc-99m-2-Methoxyisobutylisonitrile: Validation Of Differential Renal Function And Development Of A Functional Assay Of P-Glycoprotein Expression In Renal Transplant Donors

Aims: P-glycoprotein (P-gp) is a transport protein involved in drug efflux and excretion of many compounds, including cyclosporine and tacrolimus. Tc-99m-2-methoxyisobutylisonitrile (MIBI) is a P-gp substrate that has been widely used for in vivo imaging of multidrug resistance in cancer. There are limited data, however, concerning the use of MIBI for monitoring P-gp expression in diseases other than cancer. The only known mechanism of MIBI elimination from renal tubular cells involves ATP-binding cassette transporter proteins, so MIBI could potentially be used to image renal P-gp expression. The first aim of the study was to demonstrate that differential renal function (DRF), measured with MIBI in potential kidney transplant donors, was comparable to that measured with Tc-99m-MAG3. Secondly, we aimed to develop a method for quantifying renal P-gp expression using MIBI that may be useful in dose selection and predicting drug response after transplantation. Methods: Ten healthy potential donors were imaged for 20 min following iv injection of 400 MBq Tc-99m-MIBI. Further static 5-minute images were acquired at 30 and 120 min post-injection. MIBI renography was performed within 30 days of MAG3. DRF was determined as for MAG 3. Bland-Altman analysis was used to assess the agreement between DRF respectively based on MIBI and MAG3. The 2-point rate constant (k) of MIBI elimination from the kidney was calculated from the physical decay-corrected count rates recorded at 30 and 120 min in a parenchymal ROI placed over the left upper pole. The left kidney was considered more representative for analysis due to overlapping biliary and gut activity more frequently seen on the right. Results: Notwithstanding the higher administered activity, MIBI gave excellent images of renal perfusion and cortical contours that were subjectively superior to MAG3. Bland-Altman analysis demonstrated no significant difference between MIBI and MAG3 DRF (mean -0.6 +/- SD 3.9%). There was, moreover, no significant correlation between the difference and average DRF. A different pattern of elimination of the two tracers was demonstrated. In 3 donors, k was clearly lower compared to the other 7, with one having a value of zero. Conclusion: These preliminary data suggest that DRF can be accurately measured with MIBI and that the rate of renal MIBI elimination may represent an in vivo assay of renal P-gp expression. This may provide highly relevant information in the post-transplantation setting by allowing better decision making when considering therapy with drugs that are substrates for P-gp