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- 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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- Dalmo, Johanna
(författare)
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Therapy of neuroendocrine tumors with 177Lu-octreotate - Human tumor cell types and models and optimization of treatment : Terapi av neuroendokrina tumörer med 177Lu-octreotate
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neuroendocrine (NE) tumors (NET) have often metastasized at the time of diagnose, which makes it hard to cure patients with NET. Radiolabeled hormone analogues (especially somatostatin analogues, SS) can be used for diagnostics (e.g. 111In-octreotide) and therapy (e.g. 177Lu-octreotate). For development of the treatment methods, realistic tumor cell lines and models are valuable. Human NET cell lines and models are few, and there is a need to find suitable models for different types of NET, with e.g. relevant expression of hormone receptors, e.g. somatostatin receptors (SSTR), cholecystokinin-2/gastrin receptors, and catecholamine transporters. In this work, several types of human NET models (paraganglioma, gastrointestinal stromal tumor (GIST), human medullary thyroid cancer (GOT2), and midgut carcinoid (GOT1)) were studied, with the aim to evaluate the binding and/or uptake of radiolabeled hormone analogues (177Lu-octreotate, 111In-octreotide, 111In-MG0, and 131I-MIBG). Activity concentration in tumor and non-tumor tissues was measured in vitro or in vivo in different NETs. The activity concentration after 111In-octreotide injection indicated a large variation in somatostatin receptor expression in different NETs. A specific uptake and internalization of radiolabeled 111In-octreotide or 177Lu-octreotate was found in vitro in paraganglioma and in GIST, respectively, as well as a specific uptake of 131I-MIBG in paraganglioma. The tumor uptake of 111In-octreotide and 131I-MIBG in the patient with paraganglioma, and of 111In-octreotide in several individuals with GIST showed that some of these patients might benefit from radionuclide therapy. All studied human NETs in this work will serve as good models in the development of increased therapeutic effect of different NETs. 177Lu-octreotate is today routinely used for treatment of carcinoids and endocrine pancreatic tumors, but needs to be optimized. A novel treatment schedule was tested, giving a priming administration of 177Lu-octreotate before administering the therapeutic amount. This procedure resulted in higher mean absorbed dose to tumor tissue and increased therapeutic effect compared with those for a single administration. To improve the individual following-up after fractionated treatment with 177Lu-octreotate, the possibility to use urinary retinol binding protein (RBP) and valine hydantoin (VH) in blood as biomarkers for radiation induced nephrotoxicity was studied. RBP4 was shown to be a potential biomarker for nephrotoxicity, before kidney injury was demonstrated by morphology.
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- Larsson, Malin, et al.
(författare)
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Portable scintillation detector for lung activity measurements prior to V/PSPECT
- 2015
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Ingår i: Optimization in X-ray and Molecular Imaging, 28-30 May, 2015, Gothenburg, Sweden..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)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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