Research and development







Detection of tumor hypoxia with chemicalprobes

Nitroimidazole derivatives EF3 and EF5 developed by C. Koch (University of Pennsylvania, USA) offer many advantages compared with the classical compound (misonidazole) to label hypoxic cells. In particular, they lend themselves towards the development of highly specific monoclonal antibodies, which makes it possible to detect hypoxia using both flow cytometry and immunohistochemichal techniques. Beside these invasive techniques (need of biopsy material), it should be possible to develop a non invasive assay based on imaging. In this respect, coupling the compound with a positron emitter would allow to use PET to map out the hypoxic regions over the whole tumor volume and to follow up their evolution during the treatment. This study is performed in collaboration with the Laboratory of Positron Emission Tomography (TOPO) of the University. Radiobiological experiments aiming at validating the performances of EF3 and EF5 compounds for hypoxic cell detection in different tissues are in progress. Phase I clinical assays are foreseen. [supported by the "Fonds de la Recherche Scientifique Médicale" (FRSM) and the "Fonds Joseph Maisin"].

Informations : Prof. V. Grégoire, Dr. P. Mahy



Radiosensitization by nucleosideanalogues

For the last few years, our Laboratory has been interested in the association of nucleoside analogues such as fludarabine and gemcitabine with radiation. Nucleoside analogues are potent inhibitors of DNA synthesis, and as such, also inhibit the various processes involved in the repair of genomic damages induced by radiation. Presently, the following aspects are investigated: 1) demonstration of the radiosensitizing properties of gemcitabine in various mouse and human tumor cell lines; 2) elucidation of the various mechanisms of interaction between gemcitabine and radiation with emphasis on DNA DSB repair and cell synchronization; 3) correlation between the activity of deoxycytidine kinase (dck) which is the enzyme responsible for intracellular activation of gemcitabine, the concentration of the active triphosphate form of gemcitabine, and radiosensitization. In the future, up-regulation of the dck activity might be foreseen as a rationale way to increase radiosensitization by nucleoside analogues [supported by the "Fonds de la Recherche Scientifique Médicale" (FRSM) and the "Fonds Joseph Maisin"].

Informations : Prof. V. Grégoire




Informations : Dr. J.P. Machiels



Use of functional imaging with PET and MRI fortreatment planning in conformal radiotherapy of head & neck andbrain tumors.

The aim of this project is to assess the value of functional imaging for tumor volume delineation and its impact on dose distribution in 3D-conformal radiotherapy for head & neck and brain tumors. Positron Emission Tomography (PET) with [18F]-fluorodeoxyglucose and [11C]-methionine, and magnetic resonance with perfusion and diffusion algorithms are compared. All functional images are co-registered on anatomic CT and MR images. Patients are imaged before radiotherapy and during treatment before planning the boost irradiation. Validation of the various functional imaging modalities with anatomopathological examination of tumor specimens is also foreseen in patients scheduled for surgical treatment. This project is conducted by the Department of Radiation Oncology in collaboration with the Laboratory of Positron Emission Tomography (TOPO), and the Departments of Head and Neck Surgery, Oral and Maxillofacial Surgery, Nuclear Medicine and Radiology. [supported by FRSM and the Université catholique de Louvain].

Informations : Prof. V. Grégoire, Prof. G. Cosnard, Dr. M. Lonneux



Identification of molecular markers predictive oflymph node metastasis from laryngeal carcinoma

Laryngeal carcinoma can be associated with a poor prognosis and a low 5-year survival rate. The best predicator of an ominous evolution is the presence of lymph node metastasis. However, the detection of lymph node metastasis is difficult at the time of diagnosis : physical and radiological investigations are mainly based on the size of lymph nodes, which is not a reliable sign of metastasis. Accordingly, neck lymph node dissection is routinely performed whenever large lymph nodes are present to assess the prognosis of the tumour and the need for adjuvant therapy. Howeversuch a surgical procedure can have serious side effects and alternative method are highly desirable. We are attempting to identify molecular markers associated with tumour invasion and metastasis by investigating the prolifeartion of carcinomatous cells, their DNA content, and their expression ot tumour suppressor genes, of adhesion molecules and of proteinases.

Informations : Dr. M. Liu, Dr. B. Weynand, Prof. E. Marbaix



Pages: UCL School ofMedecine | RadiationOncology Dept. | Oraland Maxillofacial Surgery Dept.

Created by Dr.Pierre Mahy on August 28, 2001. Updated on September 5,2001.