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Methods that allow in situ dosimetry and range validation are essential in radiotherapy to reduce the margin of safety required to take into account the uncertainties introduced throughout the treatment workflow. This study proposes a noninvasive dose concept for carbon ion radiotherapy based on phase change ultrasound contrast agent. Injectable nanodroplets made from metastable perfluorobutane (PFB) cores stabilized with crosslinked polyvinyl alcohol shells that evaporate at physiological temperatures when exposed to carbon ion radiation (C-ion), transforming them into echo microbubbles. The nanodroplets embedded in the tissue simulation model were exposed to a 312MeV/U clinical C ion beam at a dose of 0.1-4Gy and an irradiation temperature of 37℃. By evaluating the ultrasound imaging of the bulk mode and the contrast enhancement before and after the irradiation, it was found that the significant radiation-triggered vaporization of the nanodroplet at the C ion Bragg peak was submillimeter displacement reproducible and dose-dependent. By changing the model position, beam range and scattering Bragg peak, the specific response of the nanodroplet to C ion was further confirmed. The response of nanodroplet to C ion is affected by concentration and is independent of dose rate. These early findings demonstrate the potential for a breakthrough in in vivo carbon ion dosimetry and scoping validation of polymer-shell PFB nanodroplets.
Advanced radiotherapy using beams of heavily charged particles such as protons and carbon ions (C-ions)(known as hadronic therapy) has recently become available clinically and is being developed globally with the aim of increasing the treatment of drug-resistant tumors. In addition, hadron therapy is thought to be more beneficial than traditional radiation therapy in treating cancers near critical organs, such as breast cancer on the left side near the heart. Unlikely X-ray photons, charged particles diffuse less as they penetrate tissue and store maximum energy in intervals a few millimeters wide, then stop, releasing most of their energy in a highly localized sharp distal dose drop known as Bragg peaks 3,4,5. Thus, the dose distribution obtained by using hadrons is superior to that obtained by photons due to the limited and narrow deposition range (i.e. limited lateral diffusion) of hadrons in the body. Although C ions and protons have similar physical advantages over X-rays, C ions differ from protons in radiobiological properties and are generally associated with poor prognosis and high mortality in treatment. Cornelius A. Tobias first proposed the use of carbon ions in radiation therapy, arguing that heavier ions might be more effective than protons. The main difference in the dose distribution between the two types of radiation is that the C ion has a small fragmentation tail outside of its distal decay. In addition, laterally, C – ions are characterized by a steeper decay than the proton beam, which is more conformal to the target due to the significantly narrower Bragg peak, which allows them to strike tumor masses more effectively and best preserve healthy tissue before and after the tumor. In addition, linear energy transfer (LET), which is the energy density of charged particles deposited in the material that are traversed by primary protons per unit length, 7, 8, 9.C ions induce maximum relative bioavailability (RBE) at Bragg peak, and show optimal efficacy against drug-resistant tumors at LET values of 150-200 keV/μm10 and 11. In addition, recent advances have shown that the radiobiological properties of dense ionized carbon have additional therapeutic effects in cancer therapy, enhancing immune responses and reducing angiogenesis and metastasis potential7. The interest in the clinical potential of C ions has been reflected in the increasing number of patients treated over the past two decades. Phase I and II trials in Japan have shown promising results in patients with locally advanced pancreatic cancer. Additional phase II clinical trials were recently conducted in Germany to confirm these findings 12. However, according to the Particle Therapy Collaboration Group (PTCOG), the number of active centres worldwide is still limited to 12; Mainly in Europe (Italy, Germany, Austria) and Asia (China and Japan), while 13 centers are under construction in the United States and France.
So far, one of the most critical challenges of all particle therapy options, including C-ion radiation therapy, has been
Post time: May-23-2022
