This experimental study investigates the radioactivation of titanium during proton therapy. Titanium is a commonly used material for implants. Because of its fixed position, the activation of those implants might be useful for post-irradiation field. Various titanium samples are irradiated at the West German Proton Therapy Centre Essen. The activities of the produced radionuclides are obtained with a low-level gamma-ray spectrometry system at the Dortmund Low Background Facility. Furthermore, an irradiated titanium sample is placed in a pre-clinic PET/CT scanner to investigate the potential of the implants for range verification. With the gamma-ray spectrometry technique a number of radionuclides are identified as candidates for range verification with delayed secondary gamma-rays. Furthermore, activation cross sections are calculated with the activities for the identified radionuclides. The depth distribution of the activity as obtained with the PET/CT scans has a characteristic rise towards the distal end similar to the depth dose curve.

Towards using secondary gamma-rays from proton-induced radioactivation of titanium implants for off-line field verification

• Tissues and QA devices activation is studied under clinical conditions. • Effective dose received from activation by staff are far from exceeding dose limits. • Albeit 92 μSv/h were measured in contact with patients, no restrictions are needed. 

Is neutron-activation a radiation safety issue for the facility staff and public members in proton therapy?

Proton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 μg Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1–10 μg Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field.

Zinc-Doped Iron Oxide Nanoparticles as a Proton-Activatable Agent for Dose Range Verification in Proton Therapy

Positron emission tomography (PET) for off-line field verification has been found limited by the so-called wash-out of the produced activity distribution due to biological transport processes. The activation of implants has been proposed to overcome this limitation and the general potential of titanium implants has been demonstrated in the past. Compared to implanted markers, titanium implants are used during surgical resection especially in brain tumor patients which is often performed prior to the radiotherapy treatment. An applicability test for the use of titanium implants for field verification is demonstrated. The test includes a phantom study with simple geometric phantoms and an anthropomorphic phantom. Furthermore, Monte-Carlo (MC) simulations are performed to predict the expected activity in the implants. The visual analysis reveals the general applicability for clinical implantation, while the numerical analysis of the results demonstrates the current limitations given by PET imaging and the basic physical knowledge of the activation cross sections. With the results, requirements for future generations of PET scanners for field verification in proton therapy can be derived. Necessary physics research on activation cross section can be deduced from the results. With further development in PET imaging, the incorporation of implant activation may provide an additional means for the monitoring of treatment delivery. On a qualitative basis, PET imaging of titanium implants may already be used in clinical practice for patients which come with suitable implants. Furthermore, possibly suitable implant positions can be derived from the results.

Titanium Implants for Field Verification in Proton Therapy – an Applicability Test

Direct proton range verification using oxygen-18 enriched water as a contrast agent

Several methods of proton beam range verification have been evaluated during the last decades. Since so-called in-room solutions require the space in the treatment room and offline imaging methods, e.g. positron emission tomography (PET), is limited by the wash out of biological molecules, another method is evaluated during this experimental study on the potential for PET imaging. A possible solution for the biological wash out is that, four out of five brain tumor patients at the West German Proton Therapy Centre Essen (WPE) have titanium clips from surgical resection. This requires a precise knowledge of the produced radionuclides from titanium after the irradiation with protons and the corresponding activation cross sections. For the determination of the activation cross section a pure, thin titanium sheet is irradiated. A titanium alloy, which is called grade 5 and used for implants and clips, is also irradiated and compared with the pure one. Furthermore, a first simplified titanium based phantom is irradiated and afterwards a PET scan is taken to determine the activity with the sample. The first studies show the potential of titanium for proton beam range verification.

Proton Beam Range Verification with Secondary Radiation from Titanium Implants

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Towards using secondary gamma-rays from proton-induced radioactivation of titanium implants for off-line field verification

Proton Beam Range Verification with Secondary Radiation from Titanium Implants