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Potential renal toxicity biomarkers indicating radiation injury after 177Lu-octreotate treatment

Conference contribution
Authors Johanna Dalmo
Emilie Westberg
Lisa Svedbom
Margareta Törnqvist
Lars Barregård
Eva Forssell-Aronsson
Published in Annual congress of the European association of nuclear medicine, october 19-23, 2013, Lyon, France. Posterwalk
Publication year 2013
Published at Institute of Clinical Sciences, Department of Radiation Physics
Sahlgrenska Cancer Center
Institute of Medicine, Department of Public Health and Community Medicine, Section of Occupational and environmental medicine
Institute of Medicine
Language en
Links eanm13.eanm.org/abstracts/abstract_...
Keywords Peptide receptor radionuclide therapy, nephrotoxicity, RBP, creatinine, urea, valinhydantoin
Subject categories Physical Sciences, Cancer and Oncology, Radiological physics, Radiation biology, Other Medical Sciences

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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