Abstract
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Objectives Radiation induced nephropathy is dose limiting in radionuclide therapy of neuroendocrine tumours. We investigated the nephroprotective potential of medicinal interventions after Lu-177-DOTATATE therapy in a murine model.
Methods First the appropiate therapy dose was identified. Two days after baseline scintigraphy (n=12, 12min dynamic acquisition after injection of 20MBq Tc99m-MAG3) radionuclide therapy was carried out. Four groups were assigned (Gp 1, n=6, 10MBq; Gp 2, n=8, 20MBq; Gp 3, n=7, 40MBq; Gp 4, n=7, 65MBq Lu-177-DOTATATE). Follow up scintigraphy was carried out at day 9, 23, 44 and 65. Afterwards nephroprotective potential of different drugs was evaluated. Drugs and vehicles in the control groups were applied once a day by gavage (Gp1, n=7, pravastatin 5mg/kg/d; Gp2, n=7, enalapril 10mg/kg/d; Gp3, n=8, spironolactone 6mg/kg/d; Gp 4, n=8, aqua ad inj. AND tween20; Gp 5, n=6, aqua ad inj.). Follow up scintigraphy was carried out at days 9, 23, 44, 65, 86. The “fractional uptake rate” (FUR; %/min ±SEM), which is the fractional uptake of the tracer by the kidneys and counts as a measure for renal clearance, was calculated.
Results In the first part of the study no significant in- or decrease of the FUR as compared to baseline (11.0±0.3) in the groups 1 and 2 (11.2±0.5 and 10.1±0.6, respectively) was noted. In groups 3 and 4 the FUR (8.93±0.6, p<0.05, and 6.0±0.8, p<0.01) significantly decreased. Therefore 40MBq Lu-177-DOTATATE (Gp 3) has been chosen for part two of the study. There was no significant in- or decrease of the FUR in all drug treated groups (Gp 1: 11.6±0.7; Gp 2: 11.8±0.5; Gp 3: 11.8±0.5) as compared to baseline (12.4±0.3). In contrast control groups showed significant decrease in FUR (Gp 4: 9.21±0.6, Gp 5:9.31 ±0.5; p<0.01).
Conclusions Treatment with enalapril, pravastatin and spironolactone is effective for nephroprotection during radionuclide therapy with Lu-177-DOTATATE