Molecular imaging identifies inflammatory cytokine-mediated alterations in renal tubular excretion in vivo

Objectives Various ^99mTc complexes are excreted from cells by the MRP2 transporter, which is regulated by inflammatory cytokines. This study sought to determine whether ^99mTc-MAG₃ imaging could identify effects of the inflammatory cytokines human tumor necrosis factor-α (TNF-α) & interleukin-6 (IL-6) on renal tubular excretion.

Methods Eleven F-344 rats were divided into 3 groups: Controls (n=3), TNF-α treated (n=4), & IL-6 treated (n=4). TNF-α (15µg/kg) & IL-6 (4µg/kg) were injected via tail vein 3 hrs before ^99mTc-MAG₃ scintigraphy. Data were acquired on a gamma camera equipped with a low energy high resolution parallel-hole collimator using 2.19 zoom factor. Beginning immediately after radiopharmaceutical injection, 10-sec dorsal images were acquired for 30 min using 128X128X16 matrixes. Data were analyzed on a standard clinical Nuclear Medicine workstation. Regions of interest were drawn over kidneys to obtain time-activity curves. The time to peak kidney activity (Tpeak) & per cent of Tpeak ^99mTc-MAG₃ activity remaining in the kidneys 30 min post injection (R30) were determined.

Results Tpeak of ^99mTc-MAG₃ activity was different among the 3 groups (ANOVA p = 0.001): Tpeak was delayed in IL-6 group versus Controls (6.8±3.4 min versus 1.5±0.4 min, p = 0.003). Also, Tpeak was delayed in TNF-α group versus both Controls and IL-6 group (14.7±8.0 min, p < 0.02). Moreover, R30 was different in the 3 groups: at 30 minutes Controls retained less ^99mTc-MAG₃ (26±5%) compared with IL-6 and TNF-α groups (71±18% and 75±22%, respectively), p = 0.0001, whereas the difference in the two experimental groups was not significant (p = 0.68).

Conclusions These data indicate that inflammatory cytokines affect renal clearance of ^99mTc-MAG₃, significantly delaying both uptake and clearance of this radiopharmaceutical. The ability of ^99mTc-MAG₃ imaging to demonstrate MRP2 activity suggests a role for molecular imaging in the identification and monitoring of renal inflammation in health and disease.