The future of radiotherapy

The introduction of the hadrontherapy, i.e. the employment of light nuclei beams of medium energy (few hundreds of MeV), may overcome several of the limits of conventional radiotherapy thanks to a more localized (in depth and transversally) energy deposit and a higher relative biological effectiveness. The higher physical selectivity of ion therapy demands higher precision in the monitoring of the applied treatment, especially if the target volume is located close to critical organs and a fractioned therapy is applied. In fact, minimal inaccuracies in the positioning of the patient or local anatomical changes, with respect to the information of the therapy planning X-ray CT, may produce unpredictable ions range deviations and consequently dramatic spatial changes of the planned dose. For these reasons in vivo information on the range of ions are desirable, but the complete stopping of the ions in patient prevents the application of electronic portal imaging methods as used in conventional radiotherapy.

A method for in-beam monitoring

All the ions used in hadrontherapy, protons included, induce in the biologic material nuclear reactions which led to the production of &beta⁺ emitters, i.e. mainly ¹⁵O and ¹¹C from their correspondent stable isotopes. By using other ions like carbon, oxygen or fluorine, through the fragmentation of beam ions themselves there is an additional production of other &beta⁺ emitters. The induced activity can be measured with the so-called in-beam-PET to extract in-vivo information about the effective ion path and stopping point. Through the comparison with the foreseen activity, evaluated from the dose profile stated by the treatment plan, a qualitative indication of discrepancies from the planned dose can be extracted.

The positive clinical impact of in-beam PET has been already demonstrated at GSI (Darmstadt) in case of ¹²C irradiation by using a commercial PET scanner adapted to the purpose. Thanks to fragmentation of shooted ¹²C ions themselves, the production of radioactive isotopes takes place especially in proximity of the beam stop point, i.e. in correspondence to the Bragg's Peak. Since the depth achieved by the hadronic beam depends on the beam energy itself and light ions are four times less penetrating than protons, the light ion beams suitable for radiotherapy have higher production costs. In the most part of cases, protons are consequently preferable.
The poorer spatial correlation entails a higher difficulty for the employment of a PET system for the detection of the Bragg's peak in the case of a proton beam.
However it has been recently proved that, due to the different relative biological effectiveness of proton and carbon, the intensity needed is higher with protons than with carbon ions for the target to absorb an equivalent dose. As a consequence, absorbed dose being equal, irradiation with protons induces a higher &beta⁺ activity with respect to the carbon irradiation. The higher statistic allows then one to extrapolate the Bragg's peak position with the appropriate resolution from the position of the &beta⁺ activity distal edge.

A new proton in-beam PET: DoPET

The next goal in this domain is then to demonstrate the positive clinical impact for the use of a PET system for the Bragg's peak localization in case of hadrontherapy with proton beams. In this within, a feasibility study is also in progress in our research group with the support of Pisa and Bologna divisions of INFN, for verifying the applicability of an in-beam-PET for indirect extrapolation of radiation range in tissues, in the field of proton therapy. With the DoPET project we want to perform an evaluation of detection efficiency and spatial resolution that can be achieved with a dedicated PET system, in order to propel further developments in the field of relative dosimetry. The project provides the realization of a prototype for a compact two-head PET, allowing the maximum angular cover within the volume available in the therapy room. The prototype will be used for the comparison of activity profiles obtained by measurements on phantoms and GEANT4-based simulations.

Due to the limited angular acceptance of the prototype, the exact reconstruction of the image in all the three dimension cannot be achieved. However, to the purpose of verifying the utility of an in-beam PET, the most important result is to reach resolution of the order of the millimeter for the proton range. The depth profile is in fact the most critical issue of proton therapy, while the lateral beam spread is similar for carbon ions and protons.
Each PET head will be made of a position-sensitive photomultiplier Hamamatsu H8500 coupled with a matrix of high light yield crystal pixels. The dimensions of the matrix will match those of the active area of the PMT, i.e. 49x49 mm², each pixel being 2x2 mm² large and 1.5 interaction lengths deep. In order to achieve a satisfying energetic and spatial resolution, crystal choice will be oriented towards LYSO.

The collaboration with institutes provided of medical proton beams, such as CATANA (LNS, Italy), will allow us to carry out measurements on phantoms by using the prototype built. The PET prototype, for irradiations of the order of 15 Gy, will provides counting rates lower than 20 Hz. By acquiring positron annihilation events for ten minutes, the resulting statistic will be about 10⁴ events, about one hundred times lower than that of standard PET images.

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