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An investigation on preclinical PET-based radiation therapy in a murine head and neck cancer model.
Belgium (BeMSA) - Ghent University, Ghent
Department of Diagnostic Sciences
Prof. Dr. Ingeborg Goethals
Sam Donche, Jeroen Verhoeven
Type of Research Project
- Basic science
What is the background of the project?
Head and neck squamous cell carcinoma represents 5.5% of all new cancers worldwide and causes morbidity and mortality as well as impaired quality of life due to swallowing and speech difficulties. Head and neck squamous cell carcinomas are primarily treated with surgery, radiotherapy alone, or surgery combined with postoperative adjuvant radiotherapy or chemotherapy. Hypoxia is a common feature in most of the solid tumors, including head and neck squamous cell carcinoma. Hypoxic cells can be up to three times more resistant to radiation compared to aerobic cells. A non-invasive approach using positron emission tomography (PET) and hypoxia-specific tracers can visualize the distribution of hypoxic regions in a tumor. Tumor proliferation can also be visualised by using amino acid positron emission tomography. Therefore, Fluroethyl L Tyrosine (FET) PET will be included. In this project, an orthotopic preclinical head and neck squamous cell carcinoma model will be set up and evaluated by means of PET imaging and immunohistochemical staining. If successful, the model will be used in preclinical PET-based radiotherapy studies.
What is the aim of the project?
In this study, the first objective is to investigate the feasibility of PET-based radiation therapy in a murine head and neck cancer model. A second objective is to study the overall survival of the mice between different therapy groups: Magnetic Resonance Imaging (MRI)m-based Radiotherapy (RT), FET PET-based RT, Fluoroazomycin-arabinoside (FAZA) based RT
What techniques and methods are used?
First,Squamous Cell Carcinoma Cell Line (SCCVII cells) will be grown in vitro and subsequently stereotactically inoculated in the neck of the mice. When tumor growth is confirmed, PET scans will be performed and the images will be used to set up a radiation therapy plan (data processing). When successful, preclinical radiation therapy will be executed. Mice will be followed up by measuring tumor volumes and mouse weight. The student will have the opportunity to learn more about PET tracer production and clinical routine procedures on the nuclear medicine department.
What is the role of the student?
- The student will mainly observe
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student will help with experimental planning and setup. He/she will be present during the most experiment and after observation can perform certain steps of the experiment under supervision, e.g. cell culturing, stereotactic tumor inoculation, tumor visualization (MRI, PET, computational tomography (CT)) ... The specific techniques used will depend on the schedule of the principal researchers (inoculation may already be performed prior to the arrival of the student). After the experiments the student, assisted by one of the supervisors, will help with the processing of the results. In doing so he/she will obtain skills in handling medical image data.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
No. The student will be asked to perform an extensive study of the state-of-the-art literature.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
An interest in preclinical imaging is mandatory. A certificate of animal handling (FELASA category C) is an asset but not required.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Students in biomedical fields
- Radiation therapy: dose painting and biological tumour volume  Rickhey; M.; Koelbl; O.; Eilles; C.; & Bogner; L. (2008).
- A biologically adapted dose-escalation approach; demonstrated for 18 F-FET-PET in brain tumors. Strahlentherapie und Onkologie; 184(10); 536-542.  Ling; C. C.; Humm; J.; Larson; S.; Amols; H.; Fuks; Z.; Leibel; S.; & Koutcher; J. A. (2000).
- Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. International Journal of Radiation Oncology* Biology* Physics; 47(3); 551-560. [18F]FELP and LAT1  Verhoeven; J.; Hulpia; F.; Kersemens; K.; Bolcaen; J.; De Lombaerde; S.; Goeman; J.; et al.
- Affinity evaluation of phenylalanine derivatives aimed at the LAT1 transporter in F98 glioblastoma cells. Submitted to J Nucl Med. 2018.  Wiriyasermkul; P.; Nagamori; S.; Tominaga; H.; Oriuchi; N.; Kaira; K.; Nakao; H.; ... & Endo; K. (2012).
- Transport of 3- fluoro-L-α-methyl-tyrosine by tumor-upregulated L-type amino acid transporter 1: a cause of the tumor uptake in PET. Journal of Nuclear Medicine; jnumed-112.  Kobayashi; K.; Ohnishi; A.; Promsuk; J.; Shimizu; S.; Kanai; Y.; Shiokawa; Y.; & Nagane; M. (2008).
- Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells. Neurosurgery; 62(2); 493-504.  Nawashiro; H.; Otani; N.; Shinomiya; N.; Fukui; S.; Ooigawa; H.; Shima; K.; ... & Endou; H. (2006).
- L‐type amino acid transporter 1 as a potential molecular target in human astrocytic tumors. International journal of cancer; 119(3); 484- 492. FAZA PET  A. Challapalli; L. Carroll; and E. O. Aboagye; “Molecular mechanisms of hypoxia in cancer;” Clin. Transl. Imaging; vol. 5; no. 3; pp. 225–253; 2017 SCCVII murine model  Vahle AK; Kerem A; Öztürk E; Bankfalvi A; Lang S; Brandau S.
- Optimization of an orthotopic murine model of head and neck squamous cell carcinoma in fully immunocompetent mice - Role of toll-like-receptor 4 expressed on host cells. Cancer Lett 2012;317:199–206. doi:10.1016/j.canlet.2011.11.027.  Vahle A-K; Hermann S; Schafers M; Wildner M; Kerem A; Ender O; et al.
- Multimodal imaging analysis of an orthotopic head and neck cancer mouse model and application of antiCD137 tumor immune therapy. Head Neck Cancer Ther 2015;55:1–28. doi:10.1002/hed.
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