Chromium-51 (51Cr) is an attractive radionuclide for diagnosis, which is usually applied for red cells and platelet radiolabeling. However, commercially available 51Cr produced in nuclear reactors via neutron activation requires long irradiation times and complex separation methods. In this work, five metal–organic frameworks (MIL-100 (Cr), MIL-100 (Fe), MIL-100 (Al), MIL-101 (Cr) and aluminium fumarate MOF (FuAl)) were synthesized and the effect of gamma ray irradiation with a high dose rate and a maximum dose of 6 MGy was investigated. The two chromium-based MOFs, MIL-100 (Cr) and MIL-101 (Cr), were selected as radiation targets to produce high specific activity 51Cr by the Szilard-Chalmers effect. A solid–liquid extraction was applied to extract the produced 51Cr under different conditions, including different extractants, extraction times and pH. The most promising results were achieved when using irradiated MIL-101 (Cr) and EDTA as extracting agent, reaching an enrichment factor of 1132 ± 50.@en

Radionuclide therapy employing alpha emitters holds great potential for personalized cancer treatment. However, certain challenges remain when designing alpha radiopharmaceuticals, including the lack of stability of used radioconjugates due to nuclear decay events. In this work, ultrasmall silver telluride nanoparticles with a core diameter of 2.1 nm were prepared and radiolabeled with lead-212 using a chelator-free method with a radiolabeling efficiency of 75%. The results from the in vitro radiochemical stability assay indicated a very high retention of bismuth-212 despite the internal conversion effects originating from the decay of 212Pb. To further evaluate the potential of the nanoparticles, they were radiolabeled with indium-111, and their cell uptake and subcellular distribution were determined in 2D U87 cells, showing accumulation in the nucleus. Although not intentional, it was observed that the indium-111-radiolabeled nanoparticles induced efficient tumor cell killing, which was attributed to the Auger electrons emitted by indium-111. Combining the results obtained in this work with other favorable properties such as fast renal clearance and the possibility to attach targeting vectors on the surface of the nanoparticles, all well-known from the literature, these ultra-small silver telluride nanoparticles provide exciting opportunities for the design of theragnostic radiopharmaceuticals.@en

Radionuclide therapy is an important cancer treatment modality that makes use of the local irradiation from radionuclides at the tumor sites. Radiopharmaceuticals are normally composed of three components: radionuclide, carrier and tumor targeting agent. In terms of the radionuclide carriers, macrocyclic and acyclic chelators are commonly used to complex the radiometallic ions. Besides conventional chelators, inorganic nanoparticles have also been proposed as radionuclide carriers in previous research but have been mainly focused on the diagnostic applications. In this thesis, various types of inorganic nanoparticles were radiolabeled with therapeutic radionuclides including α, β- and Auger electron (AE) emitters. The behavior of some radionuclides on the host materials during internal conversion was studied. Moreover, the cell uptake and tumor killing efficiency of the AE emitters radiolabeled nanoparticles were assessed in vitro to evaluate their potential for cancer treatment.@en

The relatively high linear energy transfer of Auger electrons, which can cause clustered DNA damage and hence efficient cell death, makes Auger emitters excellent candidates for attacking metastasized tumors. Moreover, gammas or positrons are usually emitted along with the Auger electrons, providing the possibility of theragnostic applications. Despite the promising properties of Auger electrons, only a few radiopharmaceuticals employing Auger emitters have been developed so far. This is most likely explained by the short ranges of these electrons, requiring the delivery of the Auger emitters to crucial cell parts such as the cell nucleus. In this work, we combined the Auger emitter ¹²⁵I and ultrasmall gold nanoparticles to prepare a novel radiopharmaceutical. The ¹²⁵I labeled gold nanoparticles were shown to accumulate at the cell nucleus, leading to a high tumor-killing efficiency in both 2D and 3D tumor cell models. The results from this work indicate that ultrasmall nanoparticles, which passively accumulate at the cell nucleus, have the potential to be applied in targeted radionuclide therapy. Even better tumor-killing efficiency can be expected if tumor-targeting moieties are conjugated to the nanoparticles.

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The development of clinical imaging techniques significantly improves diagnostic accuracy and provides guidance for personalized treatment of individuals. However, every single imaging modality has its distinct drawbacks that cannot fully fulfil the diagnosis requirement. Thus, rational combination of different imaging modalities can achieve more comprehensive information of disease and in this way provide better personalized treatment strategy. The hybrid PET/MRI has drawn increasing attention since its first clinical application. Imaging probes play an essential role in achieving qualified figures with accurate information of diseases. The application of nanotechnology promotes the development of versatile molecular probes for PET/MRI technique. Though there is an emerging clinical requirement, only a small number of multimodal PET/MRI probes have been investigated in preclinical research. Thus, this review tries to thoroughly summarize the nano-sized PET/MRI probes on their design, preparation and biological application. By discussing the strength and limitations of these current available PET/MRI multimodal probes, this work aims to figure out the further research direction and promote the possible clinic translation of the novel PET/MRI probes.

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Combination of therapies is a common strategy in cancer treatment. Such combined therapies only have merit provided that there is superior therapeutic outcome with fewer side effects, compared to single therapies. Here, this work explores the possibility to combine chemotherapy with radionuclide therapy using polymeric micelles as a delivery vehicle. For this purpose, this work prepares poly(ε-caprolactone-b-ethylene oxide) (PCL-PEO) micelles and load them simultaneously with paclitaxel (PTX) and ¹⁷⁷Lu(III). This work chooses a 3D tumor spheroid composed of glioblastoma cells (U87) to evaluate the combined treatment. The diffusion of the micelles in the spheroid is investigated by confocal laser scanning microscopy (CLSM) and light-sheet fluorescence microscopy (LSFM). The results show that the micelles are able to penetrate deep into the spheroid within 24 h of incubation and mainly accumulated around or in the lysosomes once in the cell. Subsequently, this work evaluates the cell killing efficiency of the single treatments (PTX or ¹⁷⁷Lu(III)) versus combined treatment (PTX + ¹⁷⁷Lu(III)) by measuring the growth of the spheroids as well as by performing a cell-viability assay. The results indicate that the combined therapy achieves a superior therapeutic outcome with better cell growth inhibition and cell killing efficiency compared to the single treatments.

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Background: Radionuclide therapy (RNT) has become a very important treatment modality for cancer nowadays. Comparing with other cancer treatment options, sufficient efficacy could be achieved in RNT with lower toxicity. β⁻ emitters are frequently used in RNT due to the long tissue penetration depth of the β⁻ particles. The dysprosium-166/holmium-166 (¹⁶⁶Dy/¹⁶⁶Ho) in vivo generator shows great potential for treating large malignancies due to the long half-life time of the mother nuclide ¹⁶⁶Dy and the emission of high energy β⁻ from the daughter nuclide ¹⁶⁶Ho. However, the internal conversion occurring after β⁻ decay from ¹⁶⁶Dy to ¹⁶⁶Ho could cause the release of about 72% of ¹⁶⁶Ho when ¹⁶⁶Dy is bound to conventional chelators. The aim of this study is to develop a nanoparticle based carrier for ¹⁶⁶Dy/¹⁶⁶Ho in vivo generator such that the loss of the daughter nuclide ¹⁶⁶Ho induced by internal conversion is prevented. To achieve this goal, we radiolabelled platinum-gold bimetallic nanoparticles (PtAuNPs) and core–shell structured gold nanoparticles (AuNPs) with ¹⁶⁶Dy and studied the retention of both ¹⁶⁶Dy and ¹⁶⁶Ho under various conditions. Results: The ¹⁶⁶Dy was co-reduced with gold and platinum precursor to form the ¹⁶⁶DyAu@AuNPs and ¹⁶⁶DyPtAuNPs. The ¹⁶⁶Dy radiolabelling efficiency was determined to be 60% and 70% for the two types of nanoparticles respectively. The retention of ¹⁶⁶Dy and ¹⁶⁶Ho were tested in MiliQ water or 2.5 mM DTPA for a period of 72 h. In both cases, more than 90% of both ¹⁶⁶Dy and ¹⁶⁶Ho was retained. The results show that the incorporation of ¹⁶⁶Dy in AuNPs can prevent the escape of ¹⁶⁶Ho released due to internal conversion. Conclusion: We developed a chelator-free radiolabelling method for ¹⁶⁶Dy with good radiolabelling efficiency and very high stability and retention of the daughter nuclide ¹⁶⁶Ho. The results from this study indicate that to avoid the loss of the daughter radionuclides by internal conversion, carriers composed of electron-rich materials should be used.

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