Gadolinium-DTPA Enhanced Dynamic MR Imaging in the Evaluation of Cisplatinum Nephrotoxicity

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Abstract
Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced dynamic magnetic resonance (MR) imaging was used to monitor the nephrotoxic effects of cis-platinum (cis-diamminedichloroplatinum; CDDP), a chemotherapeutic agent that produces damage in the proximal convoluted tubule. Ten New Zealand white rabbits (NZWs) were divided into two groups and were evaluated at two clinically relevant doses of CDDP. Group 1 (four NZWs) received CDDP intravenously at 125 mg/m2 over 1 h. Rabbits in Group 2 (six NZWs) were infused with CDDP at 40 mg/m2 each day for 5 consecutive days. Dynamic MR images were performed in the axial plane at 1.5 T using a gradient recalled acquisition in the steady state sequence with an echo time of 11 ms, a repetition time of 20 ms, and a flip angle of 10° after a bolus injection of Gd-DTPA 0.1 mmol/kg. Thirty-two sequential post Gd-DTPA images (5.12 s/image) were obtained over 2 min 45 s at a single location. All rabbits underwent baseline normal and serial post CDDP Gd-DTPA enhanced dynamic MR scans. Analysis of the alterations in the normal pattern of renal enhancement caused by CDDP was facilitated by using a stacked profile image and quantitative region of interest measurements of signal intensity. Normally, after the injection of Gd-DTPA, a dark band promptly appears in the outer cortex of the kidneys and migrates centripetally toward the papilla, reflecting the tubular concentration of Gd-DTPA. In Group 1 rabbits, nephrotoxicity due to CDDP was observed as early as 9 h after administration of the drug, with a complete disappearance of the dark band by 7 days. In Group 2 rabbits, the band disappeared gradually and reappeared 2–10 days after the completion of CDDP treatment, indicative of tubular damage and recovery with return of the concentrating ability of the kidney. These results illustrate the feasibility of using Gd-DTPA dynamic MR as a sensitive monitor of drug induced alterations of renal function.