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Coming dissertations at MedFak

  • Radiolabelled affibody molecules for imaging EGFR expression in tumours Author: Maryam Oroujeni Link: Publication date: 2021-04-22 13:45

    Affibody molecules are promising scaffold-based targeting proteins for radionuclide imaging and cancer therapy. This thesis is based on 5 original research articles (Papers I-V), with the primary focus being placed on the optimization of molecular design of EGFR-binding affibody variants for high contrast imaging of epidermal growth factor receptor (EGFR) expression in tumours. The goal of my studies was to investigate the effect of labelling chemistry on the targeting properties of the anti-EGFR affibody molecule ZEGFR:2377 labelled with technetium-99m (99mTc) for single-photon emission computed tomography (SPECT), gallium-68 (68Ga), zirconium-89 (89Zr) and gallium-66 (66Ga) for positron-emission tomography (PET) to select radiolabelled variants providing the best imaging contrast.

    In Paper I, we showed the feasibility of stably labelling the anti-EGFR affibody molecule ZEGFR:2377 with 99mTc using a peptide-based cysteine-containing chelator and evaluated the imaging of EGFR expression in tumours using the [99mTc]Tc-ZEGFR:2377 affibody molecule.

    In Paper II, the effect of the composition of cysteine-containing peptide-based chelators on the biodistribution of 99mTc-labelled anti-EGFR affibody molecules was investigated. We evaluated whether the use of glutamate-based chelators improved the imaging properties of 99mTc-labelled ZEGFR:2377.

    In Paper III, the use of cyclic (FSC) versus noncyclic chelators (DFO) as bifunctional chelators for radiolabelling the anti-EGFR affibody molecule ZEGFR:2377 with 89Zr was investigated. The in vitro and in vivo properties of the resulting DFO- and FSC-ZEGFR:2377 molecules labelled with 89Zr were studied.

    In Paper IV, the targeting properties of [68Ga]Ga-DFO-ZEGFR:2377 were evaluated and compared directly with the properties of [89Zr]Zr-DFO-ZEGFR:2377 at 3 h after injection.

    In Paper V, the targeting properties of [66Ga]Ga-DFO-ZEGFR:2377 were evaluated and compared directly with the properties of [68Ga]Ga-DFO-ZEGFR:2377 and [89Zr]Zr-DFO-ZEGFR:2377 at 3 and 24 h after injection, respectively.

  • Understanding Opioid Therapy in Chronic Pain : Assessment, Lived Experience and Conceptions Author: Hanna Ljungvall Link: Publication date: 2021-04-21 10:49

    The overarching aim of this thesis was to improve the understandings of opioid therapy for chronic non-cancer pain (CNCP) by examining the feasibility of different assessment methods of substance use, and opioid use disorder (OUD), and exploring the sense-making of opioid therapy in CNCP.  

    Methods: In study I, the reliability of the Addiction Severity Index Self-Report form (ASI-SR) was assessed by the agreement (intraclass correlation (ICC)) between the composite scores (CS) of the ASI interview and the ASI-SR, internal consistency of the CS subscales measured with Cronbach’s α, and sensitivity and specificity of the alcohol and drug CS’s, using Receiver Operating Characteristics analyses. Study II was a feasibility study of the U-PAIN cohort. Cohen’s к, PABAK, and ICC were used to assess the agreement between self-reported data on opioid use and data from medical records. In study III, interpretative phenomenological analysis was used to explore the lived experience of managing CNCP with opioids. In Study IV, phenomenography was used to explore physicians’ understandings of prolonged opioid prescribing practices.

    Results: In study I, 6/7 domains the ICC for the ASI interview and ASI-SR were good to excellent. Internal consistency was acceptable for 5/7 of the domains. Alcohol- and drug CS’s predicted clinical substance dependence diagnoses. In study II, the agreement between self-reported opioid use and prescribed dose, and the agreement between OUD according to DSM-5 and clinical ICD-10 opioid dependence diagnoses, were almost perfect. In study III, opioids were used to regain control over the pain, but opioid use could also be experienced as a downward spiral of pain, dependence, and stigmatization. In study IV, specifics of a patient could justify opioid therapy. Insufficient follow-up, ignorance about pain management and opioids, an obligation to treat patients’ pain, and lack of alternative treatments, were understood to drive continued opioid prescribing practices. 

    Conclusion: The studies suggest that the examined assessment methods of self-reported opioid use were feasible for assessing patterns of opioid use. To manage CNCP pain with opioids was experienced and conceptualized as a balancing act between pain control and quality of life, and aversive effects of opioids, e.g., OUD and stigmatization. 

  • Getting a Say : Bringing patients’ views on benefit-risk into medical approvals Author: Karin Schölin Bywall Link: Publication date: 2021-04-21 09:18

    The focus of this thesis is a new quantitative approach to consider patient preferences on benefits and risks in medical approvals. The overall aim of this thesis was to explore how patient preference information may be relevant to regulatory marketing authorisation decisions.

    Study I provides an overview of the different decision-processes of industry, regulatory agencies and health technology assessment bodies/reimbursement agencies along the medical product lifecycle. In total, 15 decision points with the potential to include patient preference information were identified. 

    Study II was an exploration of the patient perspective regarding the use of patient preference information in regulatory marketing authorisation decisions. Patients emphasised the need to have a say in decisions affecting their health and to be properly informed about potential risks and benefits of medical products. 

    Study III assessed patient preferences on benefits and risks of Rheumatoid Arthritis treatments. Results revealed that patients’ preferences differed substantially. The three most important treatment attributes for patients with rheumatoid arthritis were: the probability of severe side effects, treatment effectiveness and route of administration. Those placing relatively more importance on treatment effectiveness were willing to acceptance higher risk levels of side effects. 

    Study IV aimed to determine the influence of an educational tool, compared with traditional written information on patient preferences. It was found that those respondents receiving the educational tool focused more on the potential side effects than those receiving written information. 

    Patient preference information has the potential to reveal patients’ preferences on benefits and risks with scientific rigour and can therefore be weighed against clinical data. This thesis supports the development of a structured approach to learn about patient preferences on benefits and risks in medical approvals