A new step towards an increasingly sophisticated and patient-optimised 'precision surgery' could be contributed by an in-vivo experiment on patients launched recently to validate a radio-guided surgery technique using drugs that emit beta radiation.The new technique, developed by Sapienza and INFN (Italian National Institute for Nuclear Physics), is the result of close interdisciplinary collaboration between physicists, chemists, radiopharmacists, nuclear physicians and surgeons and could become an additional tool to support the oncological surgeon during tumour removal.

Radio-guided surgery is a technique that makes it possible to identify tumour debris in real time. Using a probe, the technique detects the radiation emitted by a radioactive substance, a radiopharmaceutical containing a specific molecule that is recognised and metabolised by the receptors of the tumour cells. In this way, it is possible to check directly during the operation whether the tissues analysed are cancerous or not, and thus guide the surgeon on the sites to be removed.

The project is based on an initial idea, patented in 2013 by Sapienza, INFN and the Centro Fermi science museum, which envisaged the use of beta-radiation: a type of low-penetrating radiation composed of electrons, which, however, poses application problems due to the limited availability of radiopharmaceuticals with this type of emission.

"Being charged particles," says Riccardo Faccini, Full Professor at the Department of Physics and currently Dean of the Faculty of Mathematics, Physics and Natural Sciences, one of the inventors of the technique, "the electrons of which beta radiation is composed quickly lose their energy as a result of interactions with the other charged particles present in all the tissues of the human body. This results in the electrons being unable to leave the patient. This is what prompted us to devise an instrument that surgeons could use during operations, placing it directly on the tissues to be analysed. Although the procedure proved effective, the difficulties of administration, high costs, and the limited use of beta-drugs prompted us to look for more accessible and sustainable alternatives".

After studies conducted in collaboration with the 'Carlo Besta' Neurological Institute, the European Institute of Oncology, the Leiden University Medical Center and the Agostino Gemelli Foundation University Hospital, the choice fell on beta+ radiation, characterised by the emission of a positron, the antiparticle of the electron, and two photons, which is used daily in nuclear medicine departments for Pet (Positron Emission Tomography) diagnostic examinations.

"While beta-radiation, given its characteristics, is unsuitable for diagnostic investigations," explains Francesco Collamati, a researcher at the INFN section in Rome and the current Principal Investigator of the study, "the photons of beta+ radiation can pass unhindered through the patient's tissues, to be eventually detected by external diagnostic apparatus. Hence the widespread use in hospitals of beta+ drugs, which can therefore also be partly used for our technique."

Despite their availability, compared to beta-emitting ones, these radiopharmaceuticals present difficulties due to the abundance of photons produced not only in diseased tissues but also in all areas of the body reached by the molecule after administration, which can disrupt the signals detected by the probe. "For this reason, it is necessary to continue testing to understand and calibrate the device and to provide doctors with indications, for example, on the count levels associated with the actual presence of a tumour," Collamati concludes.  

After years of feasibility studies and ex-vivo tests, i.e. carried out on tissue samples removed from patients undergoing operations, recent experiments are now underway, with the prototype developed by Nucleomed S.r.l., at the IEO in Milan, where the technique's potential is being studied in detail on both Gastroenteropancreatic neuroendocrine tumours (Gep-Net) and prostate carcinomas, and at the "Molinette della Città della Salute di Torino" hospital, in the case of prostate tumours.

Further Information

Riccardo Faccini
Faculty of Mathematics, Physics and Natural Sciences
riccardo.faccini@uniroma1.it