A Radio-Nano-Platform for T1/T2 Dual-Mode PET-MR Imaging.

PURPOSE: This study aimed to develop a chelate-free radiolabeled nanoparticle platform for simultaneous positron emission tomography (PET) and magnetic resonance (MR) imaging that provides contrast-enhanced diagnostic imaging and significant image quality gain by integrating the high spatial resolution of MR with the high sensitivity of PET. METHODS: A commercially available super-paramagnetic iron oxide nanoparticle (SPION) (Feraheme®, FH) was labeled with the [89Zr]Zr using a novel chelate-free radiolabeling technique, heat-induced radiolabeling (HIR). Radiochemical yield (RCY) and purity (RCP) were measured using size exclusion chromatography (SEC) and radio-thin layer chromatography (radio-TLC). Characterization of the non-radioactive isotope 90Zr-labeled FH was performed by transmission electron microscopy (TEM). Simultaneous PET-MR phantom imaging was performed with different 89Zr-FH concentrations. The MR quantitative image analysis determined the contrast-enhancing properties of FH. The signal-to-noise ratio (SNR) and full-width half-maximum (FWHM) of the line spread function (LSF) were calculated before and after co-registering the PET and MR image data. RESULTS: High RCY (92%) and RCP (98%) of the [89Zr]Zr-FH product was achieved. TEM analysis confirmed the 90Zr atoms adsorption onto the SPION surface (≈ 10% average radial increase). Simultaneous PET-MR scans confirmed the capability of the [89Zr]Zr-FH nano-platform for this multi-modal imaging technique. Relative contrast image analysis showed that [89Zr]Zr-FH can act as a dual-mode T1/T2 contrast agent. For co-registered PET-MR images, higher spatial resolution (FWHM enhancement ≈ 3) and SNR (enhancement ≈ 8) was achieved at a clinical dose of radio-isotope and Fe. CONCLUSION: Our results demonstrate FH is a highly suitable SPION-based platform for chelate-free labeling of PET tracers for hybrid PET-MR. The high RCY and RCP confirmed the robustness of the chelate-free HIR technique. An overall image quality gain was achieved compared to PET- or MR-alone imaging with a relatively low dosage of [89Zr]Zr-FH. Additionally, FH is suitable as a dual-mode T1/T2 MR image contrast agent.

Radio-enhancement effects by radiolabeled nanoparticles.

In cancer radiation therapy, dose enhancement by nanoparticles has to date been investigated only for external beam radiotherapy (EBRT). Here, we report on an in silico study of nanoparticle-enhanced radiation damage in the context of internal radionuclide therapy. We demonstrate the proof-of-principle that clinically relevant radiotherapeutic isotopes (i.e. 213Bi, 223Ra, 90Y, 177Lu, 67Cu, 64Cu and 89Zr) labeled to clinically relevant superparamagnetic iron oxide nanoparticles results in enhanced radiation damage effects localized to sub-micron scales. We find that radiation dose can be enhanced by up to 20%, vastly outperforming nanoparticle dose enhancement in conventional EBRT. Our results demonstrate that in addition to the favorable spectral characteristics of the isotopes and their proximity to the nanoparticles, clustering of the nanoparticles results in a nonlinear collective effect that amplifies nanoscale radiation damage effects by electron-mediated inter-nanoparticle interactions. In this way, optimal radio-enhancement is achieved when the inter-nanoparticle distance is less than the mean range of the secondary electrons. For the radioisotopes studied here, this corresponds to inter-nanoparticle distances <50 nm, with the strongest effects within 20 nm. The results of this study suggest that radiolabeled nanoparticles offer a novel and potentially highly effective platform for developing next-generation theranostic strategies for cancer medicine.

Toward Personalized Dosimetry with 32P Microparticle Therapy for Advanced Pancreatic Cancer.

PURPOSE: To develop a Monte Carlo model for patient-specific dosimetry of 32P microparticle localized internal radionuclide therapy for advanced pancreatic cancer. METHODS AND MATERIALS: Spherical tumor geometries and a pancreatic phantom were modeled, as well as different 3-dimensional non-uniform clinical pancreatic geometries based on patient-specific ultrasound images. The dosimetry simulations modeled the dose distribution due to the energy spectrum of emitted beta particles. RESULTS: The average dose for small (3-cm diameter) and large (6-cm diameter) spherical tumors was 111 Gy (for 7.6 MBq administered activity) and 128 Gy (for 58 MBq), respectively. For the clinical 3-dimensional geometries, on the basis of patient data, the mean doses delivered to the tumor were calculated to be in the range 102 to 113 Gy, with negligible dose to the pancreas for the smallest tumor volumes. The calculated dose distributions are highly non-uniform. For the largest tumor studied, the pancreas received approximately 6% of the tumor dose (5.7 Gy). Importantly, we found that because the smallest tumor studied exhibited the most dynamic changes in volume in response to the treatment, the dose to tumor and pancreas is significantly underestimated if a static tumor volume is assumed. CONCLUSIONS: These results demonstrate the dosimetry of 32P microparticle localized internal radionuclide therapy for pancreatic cancer and the possibility of developing personalized treatment strategies. The results also highlight the importance of considering the effects of non-uniform dose distributions and dynamic change of tumor mass during treatment on the dosimetry of the tumor and critical organs.