Denis Guilloteau: Versatility for the Benefit of Patients

Trained pharmacist and subsequent brain imaging specialist Denis Guilloteau has always striven to take the fruit of his research out of the lab and into the hospital. An approach which earned him the 2017 Award of Honor from the French National Academy of Pharmacy.

Denis Guilloteau © Inserm / François Guénet
Denis Guilloteau © Inserm / François Guénet

"When I began studying pharmacy in the 1970s, I wanted to work in a biomedical analysis laboratory. Although that was before I did an internship at Tours University Hospital [Tours CHU], explains Guilloteau, a radiopharmacist specialized in brain imaging, who received the 2017 Award of Honor from the French National Academy of Pharmacy. My internship was in the functional imaging department headed by Thérèse Planiol. This world-class neuro-nuclear medicine specialist was a brilliant professional whose passion for her subject was contagious."

From that point on, Guilloteau was well and truly bitten by the imaging bug. He finished his pharmacy studies, did an additional Ph.D. thesis in pharmaceutical chemistry and went on to specialize in radioactive markers used in imaging at the National Institute for Nuclear Science and Technology (INSTN) in Saclay. Put succinctly, a radioactive atom is bound to a carrier molecule. The carrier molecule is selected according to the biological parameter to be measured (breathing, breakdown of sugars, etc.) and its fate in the body is tracked based on the particles emitted by the tracer.

The young researcher then returned to Tours CHU, which was ahead of its time in more than one way. "The members of the team had varied backgrounds: grandes écoles, engineers, pharmacists, doctors…, he emphasized. In addition, some had expertise in several fields, such as Léandre Pourcelot, who was an engineer and medical doctor, and whose work on ultrasound was already world-renowned" Pourcelot had brought to Tours the first European Doppler ultrasound for the study of blood flow. This machine works by bouncing ultrasound waves off red blood cells: the frequency variations in the waves reflected determine the speed of blood flow. In 1972, Dr. Pourcelot developed one of the first real-time ultrasound systems that revolutionized the monitoring of pregnancies, most notably. A pioneer then, but not just in science.

To showcase his research, he created the company Delalande Électronique with the pharmaceutical company of the same name in 1968. An initiative that left its mark on Guilloteau, who went on to become not only a researcher but also head of in vitro nuclear medicine at Tours CHU, co-founder of the Center for Study and Research on RadioPharmaceuticals (CERRP) with the company Cyclopharma, and lecturer.

"Thanks to imaging, we took a biological approach to psychiatry"

A path reflecting the values from his early years with Thérèse Planiol's group. "The team’s keyword was excellence but it was imbued with benevolence. Léandre Pourcelot gently guided us to where he wanted to be, he remembers. So, when he created an Inserm unit in 1988, I followed him. I replaced him as head of that unit in 2004, without changing the founding principles." Indeed, the unit combined research and clinical practice from day one because it was co-directed by Pourcelot and the psychiatrist Gilbert Lelord. "Thanks to imaging, we took a biological approach to psychiatry. It was because of this that they were among the first to prove that mothers are not responsible for their children being autistic", he reminds us.

"Then, over the years, we became interested in neurodegenerative diseases such as Alzheimer’s, amyotrophic lateral sclerosis (ALS), Parkinson’s...", he continues. The objective was to find means of visualizing brain function – and dysfunction. The team went on to develop a number of tracers, including one of the most commonly used today: PE2I. This radioactive carbon (carbon-11) labeled molecule, developed in 1998 by Guilloteau and his colleague Patrick Emond – whose initials it bears – is used to trace dopamine.

This neurotransmitter is a key element in the communication between the dopaminergic neurons in our brain, the destruction of which is responsible for Parkinson’s disease. "Since then, for more efficacy, we have developed more than ten dopamine tracers, of which the latest, LBT-999, is being tested in patients. As always, our objective is for this tracer to be used in the clinical setting”, emphasizes Guilloteau, who remains a researcher, hospital practitioner and fervent supporter of bringing public structures and industry closer together.

It was with this mindset that he founded CERRP with Cyclopharma CEO Jean-Bernard Deloye in 2006. A partnership that led most notably to the establishment of a cyclotron in Tours. This particle accelerator, which is used to obtain radioactive atoms such as fluorine-18 or carbon-11, facilitated, for example, the development of tracer AV45 used in Alzheimer’s disease. A pathology which is due in part to the abnormal accumulation of a protein called “beta-amyloid peptide” between the neurons. Prior to the development of AV45 by US researcher Hank F. Kung at the University of Pennsylvania in the mid-2000s, these amyloid plaques could only be observed during autopsy. This tracer was produced for the first time in Europe by CERRP, which enabled its testing from 2011 in patients in France and which helped bring it to market in 2015.

The decision by Kung to entrust this production to CERRP also illustrates Guilloteau’s interest in international collaborations. "I’m not particularly drawn to travel but I do like to meet different people, which led me over twenty years ago to work with Hank F. Kung, or with Christer Halldin at Stockholm’s Karolinska Institute, with whom I worked on various tracers, from PE2I to LBT-999. Over the years, they have become very close friends, he explains. Likewise, I enjoyed teaching INSTN and European program students, and hosting young researchers. The differences in origin, culture, experience… are always enriching. "

"I couldn’t have been only researcher, pharmacist or lecturer"

And the transmission of knowledge – a real pleasure, he might add. "I taught at the faculties of pharmacy and medicine, particularly students in their early years of study. They are obsessed with the competitive examinations but by livening up classes and making them a bit theatrical, it is possible to communicate our passion, demonstrate that the prospects are vast and that, as long as they hang on in there, there is more than one path, he emphasizes. I admit that it wouldn’t have been possible for me to be a straightforward researcher, pharmacist or lecturer… and the same goes for my retirement. "

And we can certainly take his word for it! Last year, he handed the reins of the Inserm unit to Catherine Belzung. On August 30, he will definitively leave Tours CHU, but the adventure does not stop there. His next objective? Help implant imaging tools in Senegal, Burkina Faso, Ivory Coast and Togo according to his credo that "experience can be useful".