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- Dalmo, Johanna, et al.
(author)
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Potential renal toxicity biomarkers indicating radiation injury after 177Lu-octreotate treatment
- 2013
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In: Annual congress of the European association of nuclear medicine, october 19-23, 2013, Lyon, France. Posterwalk.
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Conference paper (other academic/artistic)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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- Larsson, Malin, et al.
(author)
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Portable scintillation detector for lung activity measurements prior to V/PSPECT
- 2015
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In: Optimization in X-ray and Molecular Imaging, 28-30 May, 2015, Gothenburg, Sweden..
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Conference paper (other academic/artistic)abstract
- Ventilation and perfusion SPECT (V/PSPECT) is a tomographic imaging method using 99mTc labeled carbon particles (technegas) and 99mTc-macro aggregated albumin (MAA), respectively, for examination of the lungs. The primary purpose of V/PSPECT is to diagnose pulmonary embolism (PE). Today in Sahlgrenska University Hospital, the gamma camera is used for determination of enough inhaled technegas before the ventilation SPECT, a sufficient activity in the lungs are 20- 30 MBq. To economize with camera time and eliminate the risk of contamination of the camera detector system it would be advantageous to use a portable detector in a preparation room to ensure an adequate count rate. The aim of this study was to find a method to use a portable scintillation detector for estimation of inhaled techegas in lung tissue before V/PSPECT and to validate the method for clinical use. A scintillation detector (SSL Radhound with SS404 Al probe, Southern Scientific UK, Gamma Data AB, UK), was positioned over and/or laterally of the patient lying on a bed in supine positon. The patient inhaled technegas and the countrate of the portable detector was compared to the total counts from the ventilation SPECT images. The scintillation detector count statistics showed potential to replace the gamma camera measurements of the inhaled lung activity. The detected counts by scintillation detector showed good correlation to the number of counts in the SPECT images. In conclusion, the scintillation measurements can replace the method using a gamma camera for the activity uptake measurement before ventilation SPECT in the clinic.
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- Spetz, Johan, et al.
(author)
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Effects of internal irradiation from 177Lu-octreotate on transcriptional expression in GOT1 midgut carcinoid in nude mice
- 2014
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In: SweRays Workshop, Malmö, Sweden, Aug 20-22.
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Conference paper (other academic/artistic)abstract
- Introduction: Neuroendocrine (NE) tumors expressing somatostatin receptors (SSTR) are often treated with 177Lu-octreotate. The treatment is highly successful in animal models, but low cure rates in clinical studies suggests optimization of treatment protocol is needed. Little is known about which cellular responses play a crucial role in neuroendocrine tumors after irradiation. It is therefore important to identify the effects of 177Lu-octreotate on biological functions for future optimization of treatment parameters and the identification of biomarkers predicting treatment response. The aim of this study was to investigate the transcriptional response of GOT1 midgut carcinoid in nude mice following 177Lu-octreotate treatment. Methods: GOT1 bearing BALB/c nude mice were i.v. injected with 15 MBq 177Lu-octreotate and tumor size was measured twice a week using calipers. Animals were killed after 1, 3, 7 or 41 days and tumor samples excised and snap frozen in liquid nitrogen. Total RNA was extracted from tumor samples and subjected to Illumina microarray expression analysis. Differential transcriptional profiles were identified by comparing treated and untreated tumor samples using Nexus Expression 3.0 software. Associated biological functions and biological pathways (according to Gene Ontology terms) were compared using Nexus Expression 3.0 and Ingenuity IPA. Results: The mean tumor volume was clearly reduced after 177Lu-octreotate treatment. Microarray analysis showed clear difference in regulation pattern between the time points. The analysis of associated biological functions revealed clear effect on cell death and survival, and cell cycle after 1, 3, and 7 days, while cellular movement and cellular development were clearly influenced after 41 days. Cellular growth and proliferation was also affected after 1 day but not at the other time points studied. Conclusions: : Analysis of the transcriptional regulation in GOT1 tumors in nude mice following 177Lu-octreotate treatment revealed responses in different cellular functions that were distinct for each time point. These findings indicate potential venues for increasing clinical effectiveness of midgut carcinoid therapy with 177Lu-octreotate.
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