Assessment of potential nephrotoxicity biomarkers after [177Lu]Lu-DOTA-(Tyr3)-octreotate administration and effects of antioxidant α1-microglobulin.

Patients with neuroendocrine tumours may receive higher total amount of [177Lu]Lu-DOTA-(Tyr3)-octreotate and achieve better tumor control if the risk of kidney toxicity could be predicted individually for each patient. One strategy for such a prediction includes the evaluation of early responding biomarkers for kidney damage during treatment to decide the number of treatment cycles. The aims of this study were to (1) evaluate if urinary RBP4, NGAL, creatinine and cystatin C levels may serve as early responding biomarkers for kidney damage, (2) assess the expression of NGAL, KIM-1, CDKN1A, S100A6 and ADIPOQ in kidney tissue to validate their use as histological indicators of toxicity, and to (3) examine the long-term effects of the proposed radioprotector α1-microglobulin (A1M) in mice exposed to [177Lu]Lu-DOTA-(Tyr3)-octreotate. Mice were injected with 90 or 150 MBq [177Lu]Lu-DOTA-(Tyr3)-octreotate with or without A1M. Urine was collected at several time-points, and the animals were sacrificed after 9 months. Urinary RBP4 increased from day 35 after injection of 150 MBq [177Lu]Lu-DOTA-(Tyr3)-octreotate, creatinine decreased from day 131 and cystatin C increased from day 223. KIM-1, CDKN1A and S100A6 showed a dose dependent kidney expression. Morphological signs of kidney injury were observed in mice injected with 150 MBq [177Lu]Lu-DOTA-(Tyr3)-octreotate. No clear kidney protective effect was detected when A1M was co-administered with [177Lu]Lu-DOTA-(Tyr3)-octreotate.