Research/Development

Research & Development

Nuclear Medicine

Positron Emission Tomography

PET is presently certainly the most booming diagnostic technology with a considerable impact in clinical oncological care. The radioactif label used is a short living cyclotron produced positron emitting isotope. The only PET radiopharmaceutical currently in clinical use is 18F-labeled deoxyglucose (FDG), which is an analogue of glucose. The FDG is avidly taken up by most types of malignant tumors as a function of the viable cell load and the proliferative activity.

 

The clinical applications include:

• diagnosis of malignancy (eg: the differentiation of a benign from a malignant lung lesion),
• staging (eg. preoperative staging of a recurrent colorectal cancer),
• restaging (eg. detection of residual disease after first line treatment in lymphoma),
• (early) assessing the efficacy of a treatment.

The major strenght of PET compared to the conventional diagnostic techniques are its high sensitivity (because of a high tumor-to-non tumor contrast and of its whole body field of view) combined with a high tumor specificity (because tracer accumulation requires tumor viability).

The major areas of developpement and research in this specific area are highlighted hereunder.

 

Assessment of the efficacy of a treatment.

The accumulation of FDG in a tumor mass depends on the number of viable cells (the tumor load) and the proliferative activity. Reducing the proliferation is the endpoint of all antitumoral drugs. It has been shown that the efficacy of a antineoplastic treatment can be predicted by the early change of FDG activity measured by PET performed shortly after the initiation of the treatment. These metabolic change is more rapid and more pronounced than the structural changes. A lot of interest has been drawn to this use of FDG-PET in patients with intestinal sarcoma receiving the new drug imatinib. In this case a PET scan performed as soon as two weeks on treatment predicts whether the patient will benefit from it or not.

Several research projects are presently running at the Bordet Institute validation of the use of this early PET response in lung cancer, multiple myeloma, Hodgkin lymphoma, advanced colorectal cancer, and head and neck cancer.

The use of PET as an early surrogate marker of therapeutic efficacy is extremely useful in the early clinical testing of newly designed anticancer drugs. The pharmaceutic industry is confronted with an increasing number of potential new cancer drugs (as a result of the increasing knowledge of the underlying molecular mechanisms of cancer) together with a significant increase of the costs involved in performing classic clinical studies. The rationale is that PET can serve as an early selector of new potent drugs, thereby increasing the success ratio in new drug developpement.

Several contract research programs are now running at the Bordet Institute where PET response assessment (performing PET before and after about two weeks of the treatment under study) is performed.

 

Somatostatin Receptor Imaging

Generator produced positron emitting radio-isotopes are getting available for the production of PET radiopharmaceuticals. This should make PET imaging less dependent of the expensive and complex cyclotron technology which is only available in large facilities.

A first generator producing Gallium-68 has been installed in the hot lab of the Bordet Institute. This isotope can be used to label octreotide, which can be used to target somatostatin receptor bearing tumors.

The use of Ga68-octreotide PET-CT will be first tested in neuro-endocrine tumors, for staging (in a preoperative setting) and follow up. In a more experimental setting the technique will be used to examine the somatostatine receptor expression of other cancers such as breast cancer and prostate cancer. Some early data indicate that the expression of somatostatin receptors in these tumors is linked to therapy response and overall prognosis.

 

PET-CT based dosimetry for radio-imunotherapy

Monoclonal antibodies (such as anti-CD20 MoAb) can be labeled with long living positron emitting isotopes (such as Zirconium). When performing whole body PET-CT imaging at multiple time points the biodistribution and the biokinetics of the administered radiolabeled antibody can be measured. These quantitative data can be then used for patient-based dosimetry. The aim of dosimetry is to better calculate the quantity of radiolabeled antibody to administer to obtain a therapeutic effect in a specific patient with acceptable toxicity (in other words: within the therapeutic window). Actual research at the Bordet Institute focuses on the radio-imunotherapy of lymphomas. This research work is being performed in collaboration with the Free University of Amsterdam, and is sponsored by Les Amis the Bordet.

 

Conventional nuclear medicine : SPECT (click here)

- Sentinel Node Scintigraphy
- Multi Drug Resistance

 

The therapeutic applications of radionuclides (click here)

- Yttrium-90 labelled microspheres

- Yttrium-90 labellled monoclonal antibodies against lymphoma