Radiation physicist-turned-radiobiologist Julie Constanzo takes us through a typical day working in a radioactive environment in a bid to better explain dose-response problems.
24 September is World Cancer Research Day, which raises awareness of the important and lifesaving work done by researchers. As part of this the EACR asked a variety of members to share a day in their life as a cancer researcher.
Name: Julie Constanzo
Place of work: Dr. Jean-Pierre Pouget Lab, French Institute of Health & Medical Research, Institut de Recherche contre le Cancer de Montpellier (IRCM), Montpellier, France
Job title: Postdoctoral Research Scientist
How long have you worked there: 1 year
My work is part of a multidisciplinary team gathering biologists, physicists, chemists and nuclear medicine physicians. Therefore, a typical day in our lab is invaluable because of its scientific exchange or by the support that each member gives to others. The overall aim of the “Radiobiology and targeted radiotherapy” research team led by Dr. Pouget is to better understand the radiobiological mechanisms that explain dose-response problems in terms of toxicity and efficacy. This will ultimately help to better select patients: find the right responders and / or identify those at risk of toxicity.
In addition to the purely radiative effects, we study non-targeted effects caused by intercellular communication (so-called bystander effects). As well as this, we study the involvement of the immune system (systemic effect) in the therapeutic response. The role of the immune response to targeted radionuclide therapy is the major focus of my research project.
Let’s start with a typical day in our lab when having in vivo experiments… the most exciting part of my job!
The radionuclide, sent from all around the world arrives in the lab around 7-8 a.m in a shielded container. Then, I start radiolabelling my antibodies. It requires prior preparation of a bioconjugate, consisting of a monoclonal antibody (mAb) covalently linked to functional organic or organometallic molecules. This then allows the binding between the monoclonal antibody and the radionuclide. This step can last between 40 minutes to 3 hours depending on the chemistry associated to the radionuclide used. Working in a radioactive environment requires safe handling of the radioactivity, rigor and precision. During this step, we are well protected against radiation.
After several quality controls, such as activity and purity measurements of the radiolabelled antibody, we can start the imaging and the therapy by injecting animals.
We have a dedicated animal housing next to an imaging facility including a µPET/CT and a µSPECT/CT. With this, we can for example: study glucose metabolism by injecting 18F-FDG; or follow a mAb tumor uptake (and whole body biodistribution) by injecting 89Zr-mAb.
This step can last 3 to 6 hours depending on the number of animals to scan. For therapy purposes, animals are injected with the radiolabelled mAb bellow the maximal tolerated activity, i.e. below a threshold of toxicity. The mAb will specifically recognize tumor cells, leading to targeted irradiation while sparing healthy tissues. However, it is currently poorly understood which mechanisms drive the upregulation of the immune system following radioimmunotherapy. Therefore, I use several syngeneic murine models to study the involvement of the immune system in radioimmunotherapy efficacy. Preliminary results demonstrated that lymphocytes T cells are required for radioimmunotherapy in vivo efficacy. It also demonstrated that a tumor presenting a high level of MHC-I expression can counterbalance the low tumor uptake of radioimmunotherapy when lacking of mAb receptors at the cell surface.
What challenges have you faced day to day?
In my PhD and several postdocs positions I challenged myself to better understand biology and develop techniques by putting it into practice in our lab. To me, one of the keys to effective learning of biology is to master general concepts before tackling specific ones.
I am so grateful to my mentor Dr. Pouget who hired me in his lab and believed in me as a future radiobiologist. I believe that we are all able to get out of our comfort zone. It is a great benefit for cancer research to combine all of our strengths. Working hard, learning what other research fields such as chemistry, mathematics or even evolution theories are studying can open new doors for future treatments or provide new patient care.
How can you get involved with World Cancer Research Day?
1. Sign the World Declaration for Cancer Research
2. On 24 September share a snapshot on social media from a day in your life as a cancer researcher: use #WorldCancerResearchDay
Click here to see more posts about a ‘Day in the Life’ of other cancer researchers.
About Julie’s research:
The emergence of new radiopharmaceuticals in the clinic for treating cancer can lead to better characterization of the radiobiological response to offer an adapted treatment to the patients. Radioimmunotherapy (RIT) combines radionuclide to a monoclonal antibody (mAb) directed against cancer cells for treating disseminated or metastatic cancer. Several studies have shown that not only irradiated cells but also long distance located cells could be decimated although not receiving radiation dose, the so-called systemic effect. My work focuses on investigating in preclinical models the role of the immune system in eradicating cancer cells following radioimmunotherapy.