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HER2-receptor quantification in breast cancer patients by imaging with ABY-025 Affibody and PET

Alhuseinalkhudhur, Ali (författare)
Uppsala universitet,Institutionen för immunologi, genetik och patologi
Lindman, Henrik, Docent (preses)
Uppsala universitet,Institutionen för immunologi, genetik och patologi
Sörensen, Jens, Professor (preses)
Uppsala universitet,Institutionen för kirurgiska vetenskaper
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Lubberink, Mark, Professor (preses)
Uppsala universitet,Institutionen för kirurgiska vetenskaper
Velikyan, Irina, Docent (preses)
Uppsala universitet,Institutionen för kirurgiska vetenskaper
Axelsson, Rimma (opponent)
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 (creator_code:org_t)
ISBN 9789151319957
Uppsala : Acta Universitatis Upsaliensis, 2024
Engelska 55 s.
Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

Nyckelord

PET
Breast cancer
HER2
Affibody
ABY-025
Molecular imaging
Kinetic modelling
Brain metastasis

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vet (ämneskategori)
dok (ämneskategori)

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