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- Silins, Isabella, 1983-, et al.
(author)
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Radiation dosimetry of para-chloro-2-[18F]fluoroethyl-etomidate:a PET tracer for adrenocortical imaging
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Other publication (other academic/artistic)abstract
- Introduction[11C]metomidate, a methyl ester analogue of etomidate, is used for positron emission tomography of adrenocortical cancer, and has been tested in recent clinical trials for lateralization in primary aldosteronism (PA). However, in PA, visualization as well as uptake quantification are hampered by the tracer’s rather high non-specific liver uptake, and its overall clinical usefulness is also limited by the short 20-minute half-life of carbon-11. Therefore, we evaluated para-chloro-2-[18F]fluoroethyl-etomidate, [18F]CETO, a fluorine-18 (T1/2=109.8 min) analogue, as a potential new adrenocortical PET tracer.ObjectivesThe aim of this study was to assess in vivo and in-human radiation dosimetry of [18F]CETO.Methods: Residence times were calculated based on uptake data from rats (n=30, biodistribution study with ex vivo measurements) as well as in vivo PET/CT in cynomolgus (n=1) and humans (n=9). OLINDA 1.1 was used to obtain absorbed doses in human organs (mGy/MBq) and effective dose (mSv/MBq).Results[18F]CETO showed a high uptake in human adrenal glands, still increasing at 90 minutes post injection. Regardless of species used for input data (rat, cynomolgus or human), adrenal glands (absorbed dose 0.093 ± 0.038 mGy/MBq based on human data) were confirmed as the dose-limiting organs. The effective dose based on human data was 18.2 μSv/MBq and varied little when using rat (18.4 μSv/MBq) or cynomolgus data (16.1 μSv/MBq). Conclusions[18F]CETO has a favourable biodistribution in humans for adrenal imaging. The effective dose for a typical clinical PET/CT examination with 200 MBq [18F]CETO is 3.6 mSv.
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- Alhuseinalkhudhur, Ali
(author)
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HER2-receptor quantification in breast cancer patients by imaging with ABY-025 Affibody and PET
- 2024
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Doctoral thesis (other academic/artistic)abstract
- Breast cancer is the most common malignancy in women worldwide. Human epidermal growth factor receptor type 2 (HER2) is overexpressed in up to 20% of breast cancer cases and is considered an important prognostic factor and a therapeutic target. With the introduction of HER2-targeted therapy, it was important to recognize patients who will likely benefit from such treatment. Immunohistochemistry staining performed on a tumor biopsy, with in situ hybridization to detect gene amplification if needed, is the current gold standard method for HER2 receptor quantification. However, in cases with multiple metastases, it is both unfeasible and impractical to perform multiple biopsies without risking higher morbidity. Molecular imaging with tracers specifically targeting HER2 receptors provides a non-invasive approach, which allows full body quantification without the serious side effects associated with invasive biopsies. The molecule of focus in this thesis work is Affibody ZHER2:2891 (ABY-025) molecule that has a high affinity and selectivity towards HER2 receptors.This thesis is based on four original articles. The first part focused on the aspect of breast cancer imaging using HER2-targeting gallium-labeled tracer 68Ga-ABY-025 in positron emission tomography (PET) and its role in predicting breast cancer outcome. The second part was to investigate the effect of different risk factors on developing brain metastasis, the overall survival and the effect of HER2-targeted treatment on breast cancer brain metastasis based on Uppsala County cancer registry.We demonstrated that HER2-binding Affibody PET kinetics can be explained using a two-tissue compartment model and SUV values correlated well with the influx rates calculated using kinetic modeling, supporting its use to measure actual HER2 receptor binding. Phase II study demonstrated the potential of 68Ga-ABY-025 PET to predict the treatment outcome more accurately compared to biopsy HER2-status that uses the traditional immunohistochemistry staining and in situ hybridization techniques. 68Ga-ABY-025 PET provided accurate staging and reduced false positive 18F-FDG PET results in HER2-positive cases. HER2-positive molecular subtypes were associated with an increased risk of developing brain metastasis. Yet, longer survival times were observed in HER2-positive subtypes receiving HER2-targeted therapy.
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- Andersson, Jonathan
(author)
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Water–fat separation in magnetic resonance imaging and its application in studies of brown adipose tissue
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Virtually all the magnetic resonance imaging (MRI) signal of a human originates from water and fat molecules. By utilizing the property chemical shift the signal can be separated, creating water- and fat-only images. From these images it is possible to calculate quantitative fat fraction (FF) images, where the value of each voxel is equal to the percentage of its signal originating from fat. In papers I and II methods for water–fat signal separation are presented and evaluated.The method in paper I utilizes a graph-cut to separate the signal and was designed to perform well even for a low signal-to-noise ratio (SNR). The method was shown to perform as well as previous methods at high SNRs, and better at low SNRs.The method presented in paper II uses convolutional neural networks to perform the signal separation. The method was shown to perform similarly to a previous method using a graph-cut when provided non-undersampled input data. Furthermore, the method was shown to be able to separate the signal using undersampled data. This may allow for accelerated MRI scans in the future.Brown adipose tissue (BAT) is a thermogenic organ with the main purpose of expending chemical energy to prevent the body temperature from falling too low. Its energy expending capability makes it a potential target for treating overweight/obesity and metabolic dysfunctions, such as type 2 diabetes. The most well-established way of estimating the metabolic potential of BAT is through measuring glucose uptake using 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET) during cooling. This technique exposes subjects to potentially harmful ionizing radiation, and alternative methods are desired. One alternative method is measuring the BAT FF using MRI.In paper III the BAT FF in 7-year olds was shown to be negatively associated with blood serum levels of the bone-specific protein osteocalcin and, after correction for adiposity, thigh muscle volume. This may have implications for how BAT interacts with both bone and muscle tissue.In paper IV the glucose uptake of BAT during cooling of adult humans was measured using 18F-FDG PET. Additionally, their BAT FF was measured using MRI, and their skin temperature during cooling near a major BAT depot was measured using infrared thermography (IRT). It was found that both the BAT FF and the temperature measured using IRT correlated with the BAT glucose uptake, meaning these measurements could be potential alternatives to 18F-FDG PET in future studies of BAT.
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