Evaluation of retinol binding protein 4 and carbamoylated haemoglobin as potential renal toxicity biomarkers in adult mice treated with 177Lu-octreotate

Abstract

BackgroundThe kidneys are regarded as one of the main dose-limiting organs in the treatment of neuroendocrine tumours with 177Lu-[DOTA0, Tyr3]-octreotate (177Lu-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 177Lu-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 177Lu-octreotate treatment.MethodsAdult BALB/c nude mice were injected with 60 MBq or 120 MBq of 177Lu-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.ResultsThe 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.ConclusionsUrinary 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.Trial registrationID 326-2008

Kinetic modelling of an environmentally friendly carbamazepine synthesis via urea and iminostilbene in batch and continuous processes

“…The intermediate reaction has been suggested to be reversible in the literature (Rxn 2). 41 This fits the data from this study because an increased amount of ammonium in the system will shift this equilibrium toward urea decreasing the concentration of cyanate and thus decreasing the rate of Rxn 3. It has also been observed that CBZ will break down to form ISB in acetic acid without the presence of any other reagents, and so reaction (4) has been included in the network.…”

Folate receptor-targeted radionuclide therapy: preclinical investigation of anti-tumor effects and potential radionephropathy

“…It would clearly be of great benefit to determine a plasma parameter or marker in the urine, which would allow identification of renal injury at an early stage after radionuclide therapy. In this respect the retinol binding protein 4 may be a useful marker as recently demonstrated [30].…”

Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update

“…In a population of type 2 diabetics with and without CKD, serum retinol binding protein was however not related to carotid intima thickness [ 498 ]. On the other hand urinary retinol binding protein was inversely related to kidney function and cardiovascular risk factors [ 499 ] and was also increased in proportion with the degree of renal radiation damage in mice [ 500 ].…”