First-in-Humans Application of 161Tb: A Feasibility Study Using 161Tb-DOTATOC.

161Tb has decay properties similar to those of 177Lu but, additionally, emits a substantial number of conversion and Auger electrons. The aim of this study was to apply 161Tb in a clinical setting and to investigate the feasibility of visualizing the physiologic and tumor biodistributions of 161Tb-DOTATOC. Methods:161Tb was shipped from Paul Scherrer Institute, Villigen-PSI, Switzerland, to Zentralklinik Bad Berka, Bad Berka, Germany, where it was used for the radiolabeling of DOTATOC. In 2 separate studies, 596 and 1,300 MBq of 161Tb-DOTATOC were administered to a 35-y-old male patient with a metastatic, well-differentiated, nonfunctional malignant paraganglioma and a 70-y-old male patient with a metastatic, functional neuroendocrine neoplasm of the pancreatic tail, respectively. Whole-body planar γ-scintigraphy images were acquired over a period of several days for dosimetry calculations. SPECT/CT images were reconstructed using a recently established protocol and visually analyzed. Patients were observed for adverse events after the application of 161Tb-DOTATOC. Results: The radiolabeling of DOTATOC with 161Tb was readily achieved with a high radiochemical purity suitable for patient application. Planar images and dosimetry provided the expected time-dependent biodistribution of 161Tb-DOTATOC in the liver, kidneys, spleen, and urinary bladder. SPECT/CT images were of high quality and visualized even small metastases in bones and liver. The application of 161Tb-DOTATOC was well tolerated, and no related adverse events were reported. Conclusion: This study demonstrated the feasibility of imaging even small metastases after the injection of relatively low activities of 161Tb-DOTATOC using γ-scintigraphy and SPECT/CT. On the basis of this essential first step in translating 161Tb to clinics, further efforts will be directed toward the application of 161Tb for therapeutic purposes.

Photocontrolled Release of Chemicals from Nano- and Microparticle Containers.

A benzoin-derived diol linker was synthesized and used to generate biocompatible polyesters that can be fully decomposed on demand upon UV irradiation. Extensive structural optimization of the linker unit was performed to enable the defined encapsulation of diverse organic compounds in the polymeric structures and allow for a well-controllable polymer cleavage process. Selective tracking of the release kinetics of encapsulated model compounds from the polymeric nano- and microparticle containers was performed by confocal laser scanning microscopy in a proof-of-principle study. The physicochemical properties of the incorporated and released model compounds ranged from fully hydrophilic to fully hydrophobic. The demonstrated biocompatibility of the utilized polyesters and degradation products enables their use in advanced applications, for example, for the smart packaging of UV-sensitive pharmaceuticals, nutritional components, or even in the area of spatially selective self-healing processes.

Curcuminoid-BF2 complexes: Synthesis, fluorescence and optimization of BF2 group cleavage.

Eight difluoroboron complexes of curcumin derivatives carrying alkyne groups containing substituents have been synthesized following an optimised reaction pathway. The complexes were received in yields up to 98% and high purities. Their properties as fluorescent dyes have been investigated. Furthermore, a strategy for the hydrolysis of the BF2 group has been established using aqueous methanol and sodium hydroxide or triethylamine.

Synthesis of d-fructose conjugated ligands via C6 and C1 and their corresponding [Ru(bpy)2(L)]Cl2 complexes.

A pyridyl triazole (pyta) modified sucrose ligand was prepared in a seven step synthesis using d-glucose as the protection group for d-fructose and starting from commercially available sucrose. After complexation with Ru(bpy)2Cl2 precursor, the sucrose-conjugated Ru complex of the general formula [Ru(bpy)2(L)]Cl2 was formed. Acidic cleavage of the d-glucose unit led to the first d-fructose conjugated metal complex viad-fructose C6 in literature. Additionally, pyta-modified d-fructose via C1 and the corresponding Ru complex were synthesized. All compounds were analyzed by Rf values, specific rotation, NMR, IR, UV/Vis and fluorescence spectroscopy, mass spectrometry and elemental analysis.

d-Fructose-Decorated Poly(ethylene imine) for Human Breast Cancer Cell Targeting.

The high affinity of GLUT5 transporter for d-fructose in breast cancer cells has been discussed intensely. In this contribution, high molar mass linear poly(ethylene imine) (LPEI) is functionalized with d-fructose moieties to combine the selectivity for the GLUT5 transporter with the delivery potential of PEI for genetic material. The four-step synthesis of a thiol-group bearing d-fructose enables the decoration of a cationic polymer backbone with d-fructose via thiol-ene photoaddition. The functionalization of LPEI is confirmed by 2D NMR techniques, elemental analysis, and size exclusion chromatography. Importantly, a d-fructose decoration of 16% renders the polymers water-soluble and eliminates the cytotoxicity of PEI in noncancer L929 cells, accompanied by a reduced unspecific cellular uptake of the genetic material. In contrast, the cytotoxicity as well as the cell specific uptake is increased for triple negative MDA-MB-231 breast cancer cells. Therefore, the introduction of d-fructose shows superior potential for cell targeting, which can be assumed to be GLUT5 dependent.