مجال التميز | تميز دراسي وبحثي + جوائز تفوقية |
البحوث المنشورة |
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البحث (1): | |
عنوان البحث: | EGFR Targeting Of [177Lu] Gold Nanoparticles to Colorectal and Breast Tumour Cells: Affinity, Duration of Binding and Growth Inhibition of Cetuximab-Resistant Cells |
رابط إلى البحث: | https://www.sciencedirect.com/science/article/pii/S1018364721002354 |
تاريخ النشر: | 10/08/2021 |
موجز عن البحث: |
Objective: Radioimmunotherapy (RIT) is a systemic therapy currently used in the treatment of patients with lymphoma. RIT complexes consist of a targeting molecule, commonly an antibody, radionuclide chelates and a linker which can be a nanoparticle platform. Nanoparticles facilitate the attachment of multiple radionuclides and targeting groups to a single complex. Here the target affinity, duration of target association and inhibition of colony formation of Cetuximab-resistant tumour cells with Cetuximab-targeted [177Lu]-AuNPs were investigated. Dose distribution in xenografts derived from EGFR-overexpressing cells was also determined. Methods: Cetuximab-targeted [177Lu]-AuNPs were generated by functionalising 15nm AuNPs with the chelator DOTA and Cetuximab and radiolabelling with 177LuCl3. KDis, a measure of affinity, was determined by competitive binding to EGFR expressing cells. Radio-sensitivity was determined in EGFR expressing tumour cells including the Cetuximab resistant cell line HCT116 using a colony formation assay. Dose distribution was measured in sections from xenografts grown in nude mice using autoradiography. Results: KDis for the complex binding to EGFR on MDA-MB-468 cells was 20nm. Loss of cell associated [177Lu] activity was biphasic with loss of about 50% of activity in about 4h. Remaining activity dissociated over a period of about 4days. HCT8 and MDA-MB-468, but not HCT116 cells were sensitive to the growth inhibitory effect of Cetuximab. However, treatment with Cetuximab-targeted [177Lu]-AuNPs inhibited colony formation in all 3 cell lines. Dose distribution across sections from xenografts was found to demonstrate a co-efficient of variation of 15%. Conclusion: Cetuximab-targeted [177Lu]-AuNPs demonstrate high affinity for EGFR and could be an effective treatment for Cetuximab-resistant colorectal cancer cells. A strategy involving pre-treatment with receptor targeted[177Lu] to improve RIT therapeutic ratios has the potential to enhance clinical outcomes. |
المؤتمرات العلمية |
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المؤتمر (1): | |
عنوان المؤتمر: | International Conference on Radiation Oncology, Radiobiology and Medical Physics ICRORMP 2021 |
تاريخ الإنعقاد: | 20-21/05/2021 |
مكان الإنعقاد: | Vancouver, Canada |
طبيعة المشاركة: | Oral presentation |
عنوان المشاركة: | Tumour Radionuclides Therapy: in vitro and in vivo Dose Distribution Study |
ملخص المشاركة: | Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials. |
الرابط: | https://waset.org/radiation-oncology-radiobiology-and-medical-physics-conference-in-may-2021-in-vancouver |
المؤتمر (2): | |
عنوان المؤتمر: | 27th Congress of The European Association for Cancer Research 2021 |
تاريخ الإنعقاد: | 09-12/06/2021 |
مكان الإنعقاد: | Turin, Italy |
طبيعة المشاركة: | Poster presentation |
عنوان المشاركة: | Gene Expression Profiling of Hypoxia in Bladder Cancer Cell Lines |
ملخص المشاركة: | Hypoxic tumours are resistant to radiotherapy (RT) and chemotherapy. Hypoxia modification enhances overall survival of muscle invasive bladder cancer (MIBC) patients treated with RT. The West 24-gene prognostic hypoxia gene expression signature predicts patient benefit from hypoxia modification but has not been verified as a hypoxia-sensitive biomarker in vitro. The study aimed to investigate the effect of changing oxygen levels on (1) 24-gene signature hypoxia scores (HS), (2) widely studied hypoxia-associated genes (CA9, VEGFA) and (3) genes associated with bladder cancer subtypes (EGFR, ERBB2, FGFR3). |
المؤتمر (3): | |
عنوان المؤتمر: | 1st International Workshop on Radiobiology of Molecular Radiotherapy |
تاريخ الإنعقاد: | 17/03/2021 |
مكان الإنعقاد: | Saïx, France |
طبيعة المشاركة: |
Poster presentation |
عنوان المشاركة: | Cancer Targeted Therapy: Heterogeneity of Dose Distributions In Breast And Colon Cancer |
ملخص المشاركة: | Targeted radiotherapy is an alternative radiation cancer treatment to external beam radiotherapy. Gold nanoparticles (AuNs) have been used as a vehicle in several clinical applications – via surface modification- to deliver the radiation to target specific receptors expressed on cancer cells and enhance dose-distributions of targeted radionuclides. However, heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. This study aimed to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (177Lu and 90Y) in breast cancer cells produced homogeneous dose distributions. In addition the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs was examined in breast and colorectal cancer cells in vitro and in vivo. |
جوائز التكريم |
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الجائزة (1): | |
مسمى الجائزة: | IRC 2021 XV. International Research Conference Certificate of Best Presentation Award |
الجهة المانحة: | Conference committee |
تاريخ الجائزة: | 21/05/2021 |
مجال التكريم: | Best Presentation entitled “Tumour Radionuclides Therapy: in vitro and in vivo Dose Distribution Study” in the 23rd International Conference on Radiation Oncology, Radiobiology and Medical Physics |
الجائزة (2): | |
مسمى الجائزة: | Best 1st Year Talk In “Overcoming A Research Challenge” |
الجهة المانحة: | School of Medicine, Medical Sciences and Nutrition, University of Aberdeen |
تاريخ الجائزة: | 21/06/2019 |
مجال التكريم: | Prize for the best first year talk in “Overcoming a Research Challenge” at the postgraduate Research Conference Summer 2019 held in the School of Medicine, Medical Sciences and Nutrition, University of Aberdeen. |
رقيه علي محمد شبير
دكتوراه
الطب والخدمات الصحية
University of Manchester