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.

Background: The radionuclide Ga-68 is commonly used in nuclear medicine, specifically in positron emission tomography (PET). Recently, the interest in producing Ga-68 by cyclotron irradiation of [⁶⁸Zn]Zn nitrate liquid targets is increasing. However, current purification methods of Ga-68 from the target solution consist of multi-step procedures, thus, leading to a significant loss of activity through natural decay. Additionally, several processing steps are needed to recycle the costly, enriched target material. Results: To eventually allow switching from batch to continuous production, conventional batch extraction and membrane-based microfluidic extraction were compared. In both approaches, Ga-68 was extracted using N-benzoyl-N-phenylhydroxylamine in chloroform as the organic extracting phase. Extraction efficiencies of up to 99.5% ± 0.6% were achieved within 10 min, using the batch approach. Back-extraction of Ga-68 into 2 M HCl was accomplished within 1 min with efficiencies of up to 94.5% ± 0.6%. Membrane-based microfluidic extraction achieved 99.2% ± 0.3% extraction efficiency and 95.8% ± 0.8% back-extraction efficiency into 6 M HCl. When executed on a solution irradiated with a 13 MeV cyclotron at TRIUMF, Canada, comparable efficiencies of 97.0% ± 0.4% were achieved. Zn contamination in the back-extracted Ga-68 solution was found to be below 3 ppm. Conclusions: Microfluidic solvent extraction is a promising method in the production of Ga-68 achieving high efficiencies in a short amount of time, potentially allowing for direct target recycling. Graphical Abstract: [Figure not available: see fulltext.].

A variety of polymer micelles are designed for the delivery of chemotherapeutic drugs to tumors. Although the promise of these nanocarriers is very high, in the clinic the effectivity is rather limited. Determining the in vivo fate of the micelles can greatly help to improve this treatment. Here, a simple and fast chelator-free method for radiolabeling of polymer micelles composed of different block copolymers is presented, which can allow evaluating the behavior of the nanocarriers in vivo using noninvasive nuclear imaging techniques (e.g., single photon computed tomography, SPECT). The radiolabeling method consists of adding the radioisotope ions, i.e., ¹¹¹In(III), resulting in a high radiolabeling efficiencies up to 90%. The results suggest that the radiolabeling efficiency depends on two important factors: the properties of the hydrophobic block in the block copolymer composing the micelle core, and the speciation of the radiometal salts. The formation of metal hydroxides and their precipitation in the core of the micelles appears to be a key factor for high stability. Moreover, the method can be applied to radiolabel the micelles in the presence of chemotherapeutic drugs. Finally, a SPECT study shows that the radiolabeled samples are stable in vivo without any evident loss of ¹¹¹In(III).

The cerium-based metal–organic framework UiO-66 (Ce) was examined as a potential adsorbent for the ⁹⁹Mo/^99mTc generator. The results showed that the adsorbent had an outstanding adsorption performance, reaching up to 475 mg/g adsorption capacity at pH 3. An adsorption mechanism was proposed, where the adsorption was governed by hydrogen bonds, Ce-O-Mo coordination, π-anions and electrostatic interaction. Additionally, the adsorbent exhibited excellent radiation stability and good adsorption performance when radioactive ⁹⁹Mo was applied. A ⁹⁹Mo/^99mTc generator was fabricated with UiO-66 (Ce) as adsorbent and its performance was evaluated over two weeks. The elution results showed that 92 ± 3% of ^99mTc elution efficiency could be obtained with negligible cerium breakthrough, showing the great potential of UiO-66 (Ce) as adsorbent for ⁹⁹Mo/^99mTc generators.

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.

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main Body: This commentary of highlights has resulted in 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. Conclusion: Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field in various topics including new PET-labelling methods, FAPI-tracers and imaging, and radionuclide therapy being the scope of EJNMMI Radiopharmacy and Chemistry.

Four different MOFs were exposed to γrays by a cobalt-60 source reaching a maximum dose of 5 MGy. The results showed that the MIL-100 (Cr) and MIL-100 (Fe) did not exhibit obvious structural damage, suggesting their excellent radiation stability. MIL-101 (Cr) showed good radiation stability up to 4 MGy, but its structure started degrading with increasing radiation dose. Furthermore, the results showed that the structure of AlFu MOFs started to decompose at a gamma dose of 1 MGy, exhibiting a much lower tolerance to γradiation. At this radiation energy, the dominant interaction of the gamma-ray with MOFs is the Compton effect and the radiation stability of MOFs can be improved by prolific aromatic linkers, high linker connectivity, and good crystallinity. The results of this study indicate that MIL-100 and MIL-101 MOFs have a good potential to be employed in nuclear applications, where relatively high radiation doses play a role, for example, nuclear waste treatment and radionuclides production.