Towards 3D printed multifunctional immobilization for proton therapy: initial materials characterization

Purpose: 3D printing technology is investigated for the purpose of patient immobilization during proton therapy. It potentially enables a merge of patient immobilization, bolus range shifting, and other functions into one single patient-speci c structure. In this rst step, a set of 3D printed materials is characterized in detail, in terms of structural and radiological properties, elemental composition, directional dependence, and structural changes induced by radiation damage. These data will serve as inputs for the design of 3D printed immobilization structure prototypes. Methods: Using four di erent 3D printing techniques, in total eight materials were subjected to testing. Samples with a nominal dimension of 20×20×80 mm3 were 3D printed. The geometrical printing accuracy of each test sample was measured with a dial gage. To assess the mechanical response of the samples, standardized compression tests were performed to determine the Young’s modulus. To investigate the e ect of radiation on the mechanical response, the mechanical tests were performed both prior and after the administration of clinically relevant dose levels (70 Gy), multiplied with a safety factor of 1.4. Dual energy computed tomography (DECT) methods were used to calculate the relative electron density to water ρe, the e ective atomic number Ze , and the proton stopping power ratio (SPR) to water SPR. In order to validate the DECT based calculation of radiological properties, beam measurements were performed on the 3D printed samples as well. Photon irradiations were performed to measure the photon linear attenuation coe cients, while proton irradiations were performed to measure the proton range shift of the samples. The direc- tional dependence of these properties was investigated by performing the irradiations for di erent orientations of the samples. Results: The printed test objects showed reduced geometric printing accuracy for 2 materials (deviation > 0.25 mm). Compression tests yielded Young’s moduli ranging from 0.6 to 2940 MPa. No deterioration in the mechanical response was observed after exposure of the samples to 100 Gy in a therapeutic MV photon beam. The DECT-based characterization yielded Ze ranging from 5.91 to 10.43. The SPR and ρe both ranged from 0.6 to 1.22. The measured photon attenuation coe cients at clinical energies scaled linearly with ρe. Good agreement was seen between the DECT estimated SPR and the measured range shift, except for the higher Ze . As opposed to the photon attenuation, the proton range shifting appeared to be printing orientation dependent for certain materials. Conclusions: In this study, the rst step toward 3D printed, multifunctional immobilization was performed, by going through a candidate clinical work ow for the rst time: from the material printing to DECT characterization with a veri cation through beam measurements. Besides a proof of concept for beam modi cation, the mechanical response of printed materials was also investigated to assess their capabilities for positioning functionality. For the studied set of printing techniques and materials, a wide variety of mechanical and radiological properties can be selected from for the intended purpose. Moreover the elaborated hybrid DECT methods aid in performing in-house quality assurance of 3D printed components, as these methods enable the estimation of the radiological properties relevant for use in radiation therapy

Assessment of the Theranostic Potential of Gold Nanostars—A Multimodal Imaging and Photothermal Treatment Study

Gold nanoparticles offer the possibility to combine both imaging and therapy of otherwise difficult to treat tumors. To validate and further improve their potential, we describe the use of gold nanostars that were functionalized with a polyethyleneglycol-maleimide coating for in vitro and in vivo photoacoustic imaging (PAI), computed tomography (CT), as well as photothermal therapy (PTT) of cancer cells and tumor masses, respectively. Nanostar shaped particles show a high absorption coefficient in the near infrared region and have a hydrodynamic size in biological medium around 100 nm, which allows optimal intra-tumoral retention. Using these nanostars for in vitro labeling of tumor cells, high intracellular nanostar concentrations could be achieved, resulting in high PAI and CT contrast and effective PTT. By injecting the nanostars intratumorally, high contrast could be generated in vivo using PAI and CT, which allowed successful multi-modal tumor imaging. PTT was successfully induced, resulting in tumor cell death and subsequent inhibition of tumor growth. Therefore, gold nanostars are versatile theranostic agents for tumor therapy

Synthetic Antiferromagnetic Gold Nanoparticles as Bimodal Contrast Agents in MRI and CT—An Experimental In Vitro and In Vivo Study

The use of multimodal contrast agents can potentially overcome the intrinsic limitations of individual imaging methods. We have validated synthetic antiferromagnetic nanoparticles (SAF-NPs) as bimodal contrast agents for in vitro cell labeling and in vivo cell tracking using magnetic resonance imaging (MRI) and computed tomography (CT). SAF-NP-labeled cells showed high contrast in MRI phantom studies (r2* = 712 s−1 mM−1), while pelleted cells showed clear contrast enhancement in CT. After intravenous SAF-NP injection, nanoparticles accumulated in the liver and spleen, as visualized in vivo by significant MRI contrast enhancement. Intravenous injection of SAF-NP-labeled cells resulted in cell accumulation in the lungs, which was clearly detectable by using CT but not by using MRI. SAF-NPs proved to be very efficient cell labeling agents for complementary MRI- and CT-based cell tracking. Bimodal monitoring of SAF-NP labeled cells is in particular of interest for applications where the applied imaging methods are not able to visualize the particles and/or cells in all organs