Innovative Gonio-Probe in radioguided chest surgery with PET tracers for lung cancer. Utilizzo di un innovativo Gonio-Probe nella chirurgia radioguidata del torace con traccianti PET per il tumore del polmone

Background. A leading cause of cancer deaths worldwide in both men and women is lung cancer. PET scanning is a sensitive modality for the detection of NSCLC. The major limitation of surgery in lung cancer is resection of all margins. Patients with microscopic involvement of the resection margin with tumor (R1) following seemingly complete resection have a significantly poorer prognosis than those with negative microscopic margins (R0). The optimal resection of the margins seems therefore to be a debated and fundamentally important question, which is associated with the precise operative location of the tumor. This accuracy that must be achieved is reflected in the length of the intervention, which must be as short as possible even if a very accurate procedure must be guaranteed. Different medical devices can help reduce operating times by ensuring the accuracy of tumor detection and removal of all margins. Intratumoral accumulation of the PET agent [18F]FDG can be used as a guide to identifying lesion margins of NSCLC pulmonary nodules by means of probes for radio-guided surgery, capable of detecting the high energy γ rays. The purpose of this thesis is to realize and validate a new concept, innovative probe, characterized by an active collimation system for fast radio-guided surgery, to date never conceived, using PET tracers, for the precise identification and on-going removal of the lung tumor. The goal of subsequent clinical application of this thesis is to be able to reduce operating times and to ensure negative margins in lung tumor removal, thanks to a new experimental technology of revolutionary conception. Materials and methods. A prototype of a probe for radio-guided surgery was developed. The instrument is classified in an application field between a portable gamma camera and a gamma-probes, combining a high efficiency two-dimensional view of the region of interest and a high spatial resolution. The GonioProbe comprises two integrated systems: the first one, the "Navigator", has the function to reach the gamma-rays emitting tissues, the second one, the "Lock-on-Target" system, can quickly identify the exact position of the tumor. Pre-clinical tests of the GonioProbe prototype have been performed using phantoms that reproduce the surgical theater and the position of radioactive sources (chest and lung tumor). Subsequently, tests and measurements were performed on BALB/c mice with the GonioProbe prototype. Three nude BALB/c mice (4-6 weeks old healthy female mice) were used for the experiment. The human lung cancer cell lines in the form of the solid tumor were implanted subcutaneously over the upper side of the right thigh of immune-compromised BALB/c mice. When the tumor diameters reached 6~7 mm, 250 μCi of 18F-FDG was injected intraperitoneally to the animals. The mice were scanned with the microPET (microPET Focus 120, Siemens CTI). During tests, various characteristics had been evaluated: precision in localization in terms of spatial resolution, range of radioactivity useful for the correct functioning of the instrument, instrument response time, effectiveness, time to identify the tumor lesion, accuracy in localization. Results. Mice were scanned to verify that the radiotracer is bound to the tumor tissue. The implementation of algorithms for goniometric tomography for reconstruction and visualization of images in real-time was done. The counts detected by the Gonioprobe are extremely high, this ability to effectively detect the counts is the characteristic that determines the possibility of having the directionality of the navigation system, with a short time to identify the tumor lesion. Even in most extreme conditions, the Gonioprobe, given its high sensitivity, is able to record the minimum variations in counting and to hook itself to the target after having directed the operator in the correct direction of radiation. From the statistical analysis of data collected it was determined that the expected statistical error of the Gonioprobe is less than 1 mm and therefore the Gonioprobe with respect to a commercial probe has proved to be more reliable. Conclusions. In this thesis, we have shown that thanks to the high efficiency of the GonioProbe, the amount of radioactivity to be injected in patients would be much lower than normal. Furthermore, the reduction in the time required for surgery would make it possible to further lower the dose to the operators. The problem of negative margins is fundamental, this issue could be easily solved thanks to the GonioProbe. In fact, due to the radical possibility of discriminating the lesion from the background, it will be possible to verify that there are no tissue residues in the operating bed. In conclusion, this technological advancement would allow a more effective and faster thoracic surgery in order to help the surgeon to definitively eradicate lung cancer.