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Towards a Radio-guided Surgery with $beta^{-}$ Decays: Uptake of a somatostatin analogue (DOTATOC) in Meningioma and High Grade Glioma

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 Added by Fabio Bellini
 Publication date 2014
  fields Physics
and research's language is English




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A novel radio guided surgery (RGS) technique for cerebral tumors using $beta^{-}$ radiation is being developed. Checking the availability of a radio-tracer that can deliver a $beta^{-}$ emitter to the tumor is a fundamental step in the deployment of such technique. This paper reports a study of the uptake of 90Y labeled (DOTATOC) in the meningioma and the high grade glioma (HGG) and a feasibility study of the RGS technique in these cases.



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The background induced by the high penetration power of the gamma radiation is the main limiting factor of the current Radio-guided surgery (RGS). To partially mitigate it, a RGS with beta+ emitting radio-tracers has been suggested in literature. Here we propose the use of beta- emitting radio-tracers and beta- probes and discuss the advantage of this method with respect to the previously explored ones: the electron low penetration power allows for simple and versatile probes and could extend RGS to tumours for which background originating from nearby healthy tissue makes gamma probes less effective. We developed a beta- probe prototype and studied its performances on phantoms. By means of a detailed simulation we have also extrapolated the results to estimate the performances in a realistic case of meningioma, pathology which is going to be our first in-vivo test case. A good sensitivity to residuals down to 0.1ml can be reached within 1s with an administered activity smaller than those for PET-scans thus making the radiation exposure to medical personnel negligible.
The development of the $beta^-$ based radio-guided surgery aims to extend the technique to those tumours where surgery is the only possible treatment and the assessment of the resection would most profit from the low background around the lesion, as for brain tumours. Feasibility studies on meningioma, glioma, and neuroendocrine tumors already estimated the potentiality of this new treatment. To validate the technique, prototypes of the intraoperative probe required by the technique to detect $beta^-$ radiation have been developed. This paper discusses the design details of the device and the tests performed in laboratory. In such tests particular care has to be taken to reproduce the surgical field conditions. The innovative technique to produce specific phantoms and the dedicated testing protocols is described in detail.
The $beta^-$ based radio-guided surgery overcomes the corresponding $gamma$ technique in case the background from healthy tissues is relevant. It can be used only in case a radio-tracer marked with $^{90}$Y is available since the current probe prototype was optimized for the emission spectrum of this radio-nuclide. Here we study, with a set of laboratory tests and simulations, the prototype capability in case a different radio-nuclide is chosen among those used in nuclear medicine. As a result we estimate the probe efficiency on electrons and photons as a function of energy and we evaluate the feasibility of a radio-guided surgery exploiting the selected radio-nuclides. We conclude that requiring a 0.1~ml residue to be detected within 1~s by administering 3~MBq/Kg of radio-isotope, the current probe prototype would yield a significant signal in a vast range of values of SUV and TNR in case $^{31}$Si,$^{32}$P, $^{97}$Zr, and $^{188}$Re are used. Conversely, a tuning of the detector would be needed to efficiency use $^{83}$Br, $^{133}$I, and $^{153}$Sm, although they could already be used in case of high SUV or TNR values. Finally, $^{18}$F,$^{67}$Cu, $^{131}$I, and $^{177}$Lu are not useable for radio-guided surgery with the current probe design.
Chest physiotherapy is a set of techniques, mostly empirical, used to help the draining of the mucus from the lung in pathological situations. The choice of the techniques, and their adjustment to the patients or to the pathologies, remains as of today largely empirical. High Frequency Chest Wall Oscillation (HFCWO) is one of these techniques, performed with a device that applies oscillating pressures on the chest. However, there is no clear understanding of how HFCWO devices interact with the lung biomechanics. Hence, we study idealised HFCWO manipulations applied to a mathematical and numerical model of the biomechanics of the lung. The lung is represented by an airway tree connected to an homogeneous elastic medium. We highlight that the biophysics of the idealised HFCWO is driven by two dimensionless numbers. We show that the stress applied to the mucus plays the role of a buffer for the mucus yield stress, hence reducing the amount of stress needed to mobilize the mucus. The stress is the addition of two stresses with different physical origin and of the same order of magnitude: a stress due to the airway wall deformation and a stress due to the air-mucus interactions. Our model predicts the existence of an optimal range of HFCWO working frequencies that is in agreement with the frequencies actually used during HFCWO oscillations. Moreover, our model suggests that analyzing the mouth airflow during HFCWO could allow to estimate the compliance and the hydrodynamic resistance of the lung of a patient.
A radio-guided surgery technique exploiting $beta^-$ emitters is under development. It aims at a higher target-to-background activity ratio implying both a smaller radiopharmaceutical activity and the possibility of extending the technique to cases with a large uptake of surrounding healthy organs. Such technique requires a dedicated intraoperative probe detecting $beta^-$ radiation. A first prototype has been developed relying on the low density and high light yield of the diphenylbutadiene doped para-therphenyl organic scintillator. The scintillation light produced in a cylindrical crystal, 5 mm in diameter and 3 mm in height, is guided to a photo-multiplier tube by optical fibres. The custom readout electronics is designed to optimize its usage in terms of feedback to the surgeon, portability and remote monitoring of the signal. Tests show that with a radiotracer activity comparable to those administered for diagnostic purposes the developed probe can detect a 0.1 ml cancerous residual of meningioma in a few seconds.
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