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Death receptor 5 (DR5) is overexpressed in many tumors. Combination of the anti-DR5 antibody with radionuclides such as lutetium-177 (177Lu) could enhance apoptosis and decrease the possibility of drug-induced resistance. In this study, a humanized anti-DR5 monoclonal antibody CTB006 was labeled with zirconium-89 (89Zr) and 177Lu to improve its efficiency for diagnosis and radiotherapy, respectively. The radiolabeled antibodies showed high tumor uptake in colon205 xenografts according to the results of micro-PET imaging and biodistribution. The 177Lu-DOTA-CTB006 could inhibit tumor growth significantly.

Bacterial contamination and the spread of antibiotic-resistant bacteria demand alternate methods to deal with bacterial infections. With particular advantages, photodynamic therapy (PDT) is a promising approach. As a kind of photosensitizer for PDT, light-induced antibacterial compounds like oligo

Thermodynamic equilibria of complexes of 1,3-diamino-2-hydroxypropane-N,N,N',N'-tetraacetic acid (DHPTA) with heavy lanthanides (Tb3+, Ho3+ and Lu3+) in aqueous solution have been investigated with potentiometry, spectrophotometry, luminescence spectroscopy and nuclear magnetic resonance spectroscopy (NMR). The results identified three 1:1 Ln/DHPTA (Ln: Tb3+, Ho3+ and Lu3+) complexes with different degrees of deprotonation, LnL−, Ln(H−1L)2−, and Ln(OH)(H−1L)3−, where H−1 represents the deprotonation of the hydroxyl group between two methyliminodiacetate groups in the DHPTA structure. The alkoxide form of the DHPTA hydroxyl group directly binds to the lanthanide atom, forming highly strong chelation. The complex of Ln(H−1L)2− could be present as a dimeric or polymeric complex in solution.

Photodynamic therapy (PDT) is a potential approach to resolve antibiotic resistance, and phenylene/thiophene-ethynylene oligomers have been widely studied as effective antibacterial reagents. Oligomers with thiophene moieties usually exhibit good antibacterial activity under light irradiation and dark conditions. In the previous study, we verified that neutral oligo-p-phenylene-ethynylenes (OPEs) exhibit better antibacterial activity than the corresponding cationic ones; however, whether this regular pattern also operates in other kinds of oligomers such as oligo-thiophene-ethynylene (OTE) is unknown. Also, the antibacterial activity comparison of OTEs bearing cyclic and acyclic amino groups will offer useful information to further understand the role of amino groups in the antibacterial process and guide the antibacterial reagent design as amino groups affect the antibacterial activity a lot. We synthesized four OTEs bearing neutral or cationic, cyclic, or acyclic amino groups and studied their antibacterial activity in detail. The experimental results indicated that the OTEs exhibited better antibacterial activity than the OPEs, the neutral OTEs exhibited better antibacterial activity in most cases, and OTEs bearing cyclic amino groups exhibited better antibacterial activity than those bearing acyclic ones in most cases. This study provides useful guidelines for further antibacterial reagent design and investigations.

The gastrin releasing peptide receptors (GRPRs) overexpress in various tumors, which provided the opportunity for GRPR targeted tumor radiological diagnosis and therapy. In recent reports, the GPPR antagonists presented superior specific targeting affinity over the agonists. However, antagonists suffer from many shortcomings regarding their binding affinity and biodistribution properties. In this study, we designed the dimer/trimer antagonists to address the radiotherapy requirements. The results showed both of dimer and trimer RM26 derivatives appeared a progressive improvement. This study provided an efficient strategy to improve the tumor accumulation properties for the GRPR antagonist analogs.

The purposes of this study were as follows: (1) to radiolabel ibandronic acid (IBA, a third-generation bisphosphonate) with 177 Lu, investigating optimal labeling conditions, and (2) to analyze biodistribution and imaging properties of intravenous 177 Lu-ibandronate (177 Lu-IBA) administered in animals. 177 Lu-labeled methylene diphosphonate (177 Lu-MDP) served as a comparator agent. Differing proportions of IBA solution and 177 LuCl3 solution were combined to determine an optimal ratio for radiolabeling purposes, varying pH, temperature, and time to establish ideal reactivity conditions. Radiochemical purity of the labeled compounds was then assessed by paper chromatography. In vitro and in vivo stabilities were also measured at specific time intervals. In Kunming mice, biodistributions of 177 Lu-IBA and 177 Lu-MDP and respective agent activities in various organs were monitored by gamma counter, and we performed single photon computed tomography/computed tomography (SPECT/CT) imaging of 177 Lu-IBA in normal New Zealand White rabbits. Radiolabeling yields for 177 Lu-IBA proved to be >97% within 30 minutes at 90°C, and its radiochemical purity ensured stability in vitro and in vivo. Furthermore, we found that 177 Lu-IBA is readily soluble in water, showing higher skeletal uptake than 177 Lu-MDP but lower uptake by liver and spleen. The image quality of 177 Lu-IBA was so clear that even after 6 days, analysis was still feasible.

Gastrin releasing peptide receptors (GRPRs) are one of the most interesting targets over expressed in various tumors. Due to the superior potential of the GRPR antagonist analogs, they have been studied in the tumor radio imaging and therapy field. However, typical antagonists suffered the shortcomings of no internalization and poor binding affinity which hampered their applications in radiotherapy. Therefore, we attempted to introduce Oligoarginines (cell penetrating peptides) to RM26, aiming to increase the binding affinity or even trigger the internalization of the peptides on cells. The results showed Arg6 as the most potent CPP, significantly enhanced the binding avidity of RM26 to the GRPR.

Porphyrins are used in clinic as the photosensitizers for cancer treatment. However, most porphyrins tend to form aggregates in aqueous solution due to their hydrophobicity, which results in significantly reduced photocytotoxicities. Therefore, their applications in clinic are limited. To overcome these disadvantages, drug-carriers are designed for the delivery of porphyrins. In this study, we designed the surface modified liposomes for porphyrin delivery. Four types of porphyrins were loaded in liposome separately. We systemically investigated the porphyrin-containing liposomes in terms of their physicochemical properties as well as light-responsive properties. The hyaluronic acid derivative with aldehyde group was used to modify the liposome-porphyrin via the “click” reaction in order to enhance the uptake in CD44 overexpressed cancer cells. The results showed that 10,15,20-tetrakis(4-hydroxyphenyl) porphyrin (p-OH) had highest loading efficiency. The liposomes with p-OH showed highest toxicity to the cells with or without light exposure. The uptake of hyaluronic acid (HA) coated Lip-p-OH was proved to be specific to MDA-MB-231 cells by pretreating the cells with natural HA polymer as the block agent. This study provided an efficient strategy to enhance the cytotoxicity of porphyrin in aqueous solution, and to increase the affinity of porphyrin to the cancer cells.

Positive charged porphyrins have long been regarded as effective biocidal agents, however neutral porphyrins have rarely been studied in their ability photoinactivating microbials, and the structure-activity relationship such as correlation of electronic effect and biocidal activity of porphyrins still remains unclear. Herein, four neutral porphyrins with various electronic effects were selected to undergo light-induced biocidal processes. It turned out that the TPPOH and TPPNH2 with electron-donating groups NH2 and OH, respectively, exhibited much more powerful light-induced biocidal activities against E. coli and S. aureus than TPP and TPPNO2 with electron-withdrawing group NO2. This phenomenon suggested that neutral porphyrins may be treated as a new class of biocidal agents and functional groups with various electronic effects on porphyrins can dramatically affect porphyrins' light-induced biocidal activities. Mechanistic studies demonstrate that despite a better light-induced antibacterial ability of TPPOH, its singlet oxygen generation efficacy is a little lower than that of TPPNH2, together with charge characteristics and lipophilicity, it is clear that (1) the oxidative species singlet oxygen and ROS played the key role in the photo-activated antimicrobial processes of porphyrins, and (2) higher singlet oxygen or ROS yields of TPPOH and TPPNH2 may originate from their structural characteristics, namely electron-donating groups OH or NH2, and (3) a synergistic effect of all other factors including the electrostatic and hydrophobic effects must involve in the process and cooperatively determine their biocidal activities.

The influence of the linking group between the phosphoryl and bridging moieties in phosphoryl-containing task-specific ionic liquids (TSILs) on the extraction of uranyl ions was experimentally and theoretically investigated. A novel phosphoramidate-based TSIL with an amine group as the linking moiety resulted in a higher uranyl ion extraction efficiency compared with that of other phosphoryl-based TSILs. A distribution ratio of 4999 ± 51 can be achieved for uranyl ions. The uranyl ions (76.7 ± 1.5%) were stripped from the loaded ionic liquid phase in a single stage using 0.05 M diethylenetriamine pentaacetic acid in a 1.0 M guanidine carbonate solution. The extraction stoichiometry of the uranyl ions was determined by a slope analysis of the extraction data. Furthermore, the fundamental nature of the interaction between the phosphoramidate-based TSIL and uranyl ions was theoretically studied for the first time. The theoretical calculations demonstrated that the synergistic effect of the complexation interaction and H-bond formation between the phosphoramidate-functional ionic liquid and uranyl nitrate led to the higher extraction efficiency. These results provide a basis for rational design, synthesis and potential applications of novel TSILs for uranyl extraction.

A number of oligo-p-phenylene-ethynylenes (OPEs) have exhibited excellent biocidal activity against both Gram-negative and Gram-positive bacteria. Although cell death may occur in the dark, these biocidal compounds are far more effective in the light as a result of their abilities to generate cell-damaging reactive oxygen species. In this study, the interactions of four OPEs with Escherichia coli and Staphylococcus aureus have been investigated. Compared to the OPEs with quaternary ammonium salts (Q-OPE), the OPEs with tertiary ammonium (T-OPE) effectively kill many more bacterial cells under light irradiation, presumably by severe perturbations of the bacterial cell wall and cytoplasmic membrane. According to the findings from this study, such intriguing light-induced antibacterial behavior is probably attributed to the combination of bacterial membrane disruption and the interfacial or intracellular generation of singlet oxygen or other ROS. Singlet oxygen was proved to be formed from irradiation of the OPEs, whereas the varying cell membrane perturbation abilities of OPEs enhance antibacterial activity.

Due to the low concentration of 188Re-radiopharmaceuticals, identity confirmation of the complex is generally performed only indirectly by assessment of their retention time on HPLC. Herein, LC-MS and UV spectrometer are utilized to confirm the identity of the Re-mercaptoacetyltriglycine (MAG3) complex. The main peak in LC-MS spectrum coincided with the expected ion mass of the oxorhenium (V)-MAG3 complex. Meanwhile, possibility of generation of the tin complex during the coordination process was excluded. Additionally, the simple method of radiolabelling MAG3 with 188Re was developed. All the experimental results can confirm the purity and effective specific activity of the corresponding 188Re-MAG3.

Replacing conventional solvents by ionic liquids is a promising route to greener nuclear fuel cycles. Here, we report a unique multi-functional task-specific ionic liquid (TSIL) for the extraction and separation of trace thorium (Th). The phosphoramidate substituted butyl groups to imidazolium ionic liquid (PN-TSIL) shows superior extraction ability and selectivity (distribution rations of Th ~ 8302 and separation factor of Th to uranium (U) ~ 793 at 2 mol/L HNO3). For industial application purpose, an extraction chromatographic resin perpared by PN-TSIL (called PN-TSIL Resin) was made to develop a rapid, highly specific separation technique for simulative 229Th/233U separation process. Moreover, combination of spectroscopic investigations, quantum-mechanical calculations and thermodynamic parameters mearsurment, an unprecedented resolution picture of extraction process was delineated. The extraction ability and selectivity of thorium could be explained by the multiple binding sites though hybrid interactions (coordination and hydrogen bond) between thorium and PN-TSIL, leading to an entropy-driven extraction process. The understanding of solvent extraction mechanism in molecular scale will inspire new ways for TSIL design for nuclear fuel cycles.

Hyaluronan (HA) have been widely used as the ideal biomaterials. It is important to understand their degradation and distribution for better optimization. From a new aspect of using radiotracers, we designed the HA-tyramine-bisphosphonate derivative for dual-labelling with two radionuclides (99mTc and 131I) simultaneously for in vitro and in vivo tracking. This dual-radiolabelled HA derivative can still be non-covalently crosslinked by hydroxyapatites to form injectable gel. The excellent properties of the gel, such as robust, biodegradable, and self-healing capacity were maintained. We firstly proved the possibility to distinguish different radionuclides in the degraded gel using the high-resolution gamma-ray spectrometry. The radiolabelled gel showed lower toxicity than pure hydroxyapatites against various cell lines, while the in vivo results proved that the 99mTc/131I-labelling of the gel was safe and stable enough for imaging and quantitatively tracking. The present method can also be applied for the development of dual-radiolabelled gels from other polysaccharides.

The purposes of this study were as follows: (1) to radiolabel ibandronic acid (IBA, a third-generation bisphosphonate) with