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Supervisor’s Foreword

Radio-guided surgery (RGS) represents a very useful surgical adjunct to intraop- eratively detect millimetric tumor residues. The impact of RGS on the surgical management of cancer patients includes providing the surgeon with vital, real-time information, regarding the location and the extent of disease as well as the assessment of surgical resection margins.

Therefore, RGS is crucial for those cases where a complete resection influences the recurrence-free survival and the overall survival of the patients, particularly for those tumors where the surgical mass removal is the only possible therapy. The technique makes use of a radiolabeled tracer, preferentially taken up by the tumor to mark the cancerous tissue from the healthy organs, and a specific probe system sensitive to the emission released by the tracer to identify in real time the targeted tumor loci. To allow the diffusion of the drug to the margins of the tumor, the radiopharmaceutical is administered to the patient several hours in advance.

Established methods make use of a combination of a 7-emitting tracer with a 7 radiation detection probe. Some current clinical applications of RGS are radio-immuno-guided surgery (RIGS) for colon cancer, sentinel-node mapping for malignant melanoma and breast cancer, detection of parathyroid adenoma, bone tumors (such as osteoid osteoma), and thyroid carcinoma lymph-node recurrence in the neck. A limit to the applicability of this technique comes from the high pene­tration power of the 7 radiation. This implies that an eventual uptake of the tracer in nearby healthy tissues would represent a non-negligible background, sometimes preventing the technique’s applicability, e.g., in cerebral and abdominal tumors because of the large tracer uptake from the brain, the bladder, the kidneys, the spleen, the liver, etc., and in pediatric tumors due to the short distances between organs.

To mitigate the effect of the 7 background, alternative solutions are being studied with the scope of extending the RGS to other clinical cases that could profit from this technique.

In early stages, the use of fl+decaying tracers was proposed, since they are largely diffused due to the positron emission tomography (PET). The emitted
positrons have a limited penetration and their detection is local. On the other hand, positrons annihilate with electrons in the body and produce 7s with energy of 511 keV: the background persists and actually increases in energy. The improvement, with respect to the use of pure 7-emitters, is that a dual system allows measuring the background separately and to subtract it from the observed signal. This approach has been studied in pre-clinical tests but it is not yet in use in clinical practice. The largest limitations range from the activity to be administered to achieve a quick probe response, to the sophistication of the probe and to the exposure of the medical personnel.

Alternatively, our research group is developing a novel RGS technique using fl­radiation and Francesco Collamati joined this activity in the very beginning. The main innovation of the technique is based on the low penetration of the emitted electrons. Low background from healthy tissue around the lesion allows both a smaller radiopharmaceutical absorbed dose to detect tumor remnants, and the possibility of extending the technique to cases with a large uptake from healthy organs (e.g., brain tumors, because of the large uptake of radiotracers from the healthy brain when fl +emitting tracers, like 18F-FDG, are administered). A lower exposure to the medical team is also expected.

The thesis work of Francesco Collamati covered the most important aspects of the development of the technique, from the design of the fl probe to the identification of the potentialities of the technique for tumors of clinical interest.

In particular fl-probes are made of a scintillating crystal and a light detector. Francesco Collamati started his research investigating the properties of p-terphenyl as scintillator for low energy electrons: it has a low Z, with consequently low sensitivity to photons, but high light yield. It has not been adopted prior to this study because it has a short light attenuation length, which limits the possible thickness of a p-terphenyl crystal. The energy deposition of low energy electrons was found to be compatible with the light absorption of the material.

Next, this thesis describes the efforts in developing an appropriate simulation of the expected performances of this technique in tumors expressing somatostatin receptors. A chain starting from DICOM images of PET scans of the pathologies of interest (namely meningioma, glioma and neuroendocrine tumors) and arriving to the expected number of photo electrons detected by the light detector was devel­oped with the FLUKA Monte Carlo code. A thorough understanding of the content of the images and its interface with FLUKA, the simulation of the probe and the possible tumor residual configurations was a major research endeavor.

Such effort culminated in the feasibility study of fl--RGS for brain and neu­roendocrine tumors, which warranted a press release by the American Society of Nuclear Medicine and Molecular Imaging. This study is currently being confirmed by tests on the patient that started in 2015.

Rome, Italy

Prof. Riccardo Faccini

February 2016

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Scientific source Francesco Collamati. An Intraoperative Beta-Probe for Cancer Surgery. Springer Theses Recognizing Outstanding Ph.D. Research. 2016

Other medical related information Supervisor’s Foreword:

  1. CHAPTER 2 MATERIALS AND RESEARCH METHODS, VOLUME OF OBSERVATIONS
  2. Supervisor’s Foreword
  3. INTRODUCTION