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- Dalmo, Johanna, et al.
(författare)
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Evaluation of retinol binding protein 4 and carbamoylated haemoglobin as potential renal toxicity biomarkers in adult mice treated with Lu-177-octreotate
- 2014
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 4:59
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Tidskriftsartikel (refereegranskat)abstract
- Background: The kidneys are regarded as one of the main dose-limiting organs in the treatment of neuroendocrine tumours with Lu-177-[DOTA(0), Tyr(3)]-octreotate (Lu-177-octreotate), despite the successful use of kidney uptake blocking agents such as lysine and arginine. To avoid renal toxicity but still give each patient as high amount of Lu-177-octreotate as possible, there is a need for methods/biomarkers that indicate renal injury in an early stage of the treatment. The aim of this study was to investigate the potential of using urinary retinol binding protein 4 (RBP4) and carbamoylated haemoglobin (Hb) in blood as biomarkers of nephrotoxic effects on adult mice after Lu-177-octreotate treatment. Methods: Adult BALB/c nude mice were injected with 60 MBq or 120 MBq of Lu-177-octreotate or with saline (control). Urine was collected before injection and concentrations of urinary RBP4 and creatinine were determined 14 to 90 days after injection Blood samples were collected after 90 days, and carbamoylated N-terminal valine in Hb, formed from urea, was measured as valine hydantoin (VH) after detachment from Hb. Results: The RBP4 values increased with administered activity and time. For the 60 and 120 MBq groups, statistically significantly higher RBP4 levels (p <0.05) were found at day 60 and 90 compared to baseline, also at day 30 for 120 MBq group. For VH, the mean values were similar for the 60 MBq and control groups, while a small increase was observed for the 120 MBq group; but there were no statistically significant differences between any of the groups (p >0.05). No morphological changes in the kidney tissue were found. Conclusions: Urinary RBP4 is a promising new biomarker for radiation-induced renal toxicity. For the conditions used in this experiment, carbamoylated Hb (from urea) measured as VH may not be a sufficiently sensitive biomarker to be used for renal toxicity.
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| 2. |
- Dalmo, Johanna, et al.
(författare)
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Potential renal toxicity biomarkers indicating radiation injury after 177Lu-octreotate treatment
- 2013
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Ingår i: Annual congress of the European association of nuclear medicine, october 19-23, 2013, Lyon, France. Posterwalk.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The kidneys are one of the most exposed non-tumor tissues and regarded as one of the main dose-limiting organs in peptide receptor radionuclide therapy (PRRT). [177Lu-DOTA0, Tyr3]-octreotate (177Lu-octreotate) has shown promising results in the treatment of somatostatin receptor overexpressing neuroendocrine tumors, but optimization is still needed. The ability to give each patient as much 177Lu-octreotate as possible without inducing nephrotoxicity is necessary for an efficient treatment. However, due to large inter-individual differences in uptake and retention in the kidneys, there is a need for efficient Methods that early can indicate renal injury. A possible way is to identify biomarkers for high risk of radiation nephrotoxicity. The aim of this study was to investigate the potential of using urinary retinol binding protein (RBP), and blood valinhydantoin (VH) as biomarkers of nephrotoxicity on adult mice after 177Lu-octreotate treatment. BALB/c nude mice (n=6/group) were i.v. injected with 60 MBq or 120 MBq of 177Lu-octreotate. The control group was mock treated with saline. Spot urine samples were collected before injection, and 14, 30, 60 and 90 days after injection. Analysis of RBP4 and creatinine was performed using Mouse RBP4 ELISA kit and Creatinine kit from R&D Systems, respectively. Erythrocytes were separated from whole blood samples collected 90 days after injection, and analysed for VH by LC-MS/MS. The ratio between VH and a volumetric standard was calculated. The RBP/creatinine level increased with time in both groups given 177Lu-octreotate, with earlier and higher response for the 120 MBq group. No clear change in VH level between the different groups was observed. The result show that RBP may be a promising new biomarker for radiation induced kidney toxicity. The presently used method based on VH was not sensitive enough to be used as kidney toxicity marker. Further studies on mice are ongoing to validate if RBP4 may be efficient in predicting late nephrotoxicity. In patients, RBP/creatinine levels are followed in urine samples after treatment with 177Lu-octreotate.
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