Indium-111 labeled gold nanoparticles for in-vivo molecular targeting.

The present report describes the synthesis and biological evaluation of a molecular imaging platform based on gold nanoparticles directly labeled with indium-111. The direct labeling approach facilitated radiolabeling with high activities while maintaining excellent stability within the biological environment. The resulting imaging platform exhibited low interference of the radiolabel with targeting molecules, which is highly desirable for in-vivo probe tracking and molecular targeted tumor imaging. The indium-111 labeled gold nanoparticles were synthesized using a simple procedure that allowed stable labeling of the nanoparticle core with various indium-111 activities. Subsequent surface modification of the particle cores with RGD-based ligands at various densities allowed for molecular targeting of the αvß3 integrin in-vitro and for molecular targeted imaging in human melanoma and glioblastoma models in-vivo. The results demonstrate the vast potential of direct labeling with radioisotopes for tracking gold nanoparticles within biological systems.

Biodistribution of two octreotate analogs radiolabeled with indium and yttrium in rats

In this study, two octreotate derivatives N-[4-carboxy-4-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-1-yl]butanoyl]-Tyr(3)-octreotate (DOTAGA-tate) and N-[[4,10-bis(carboxymethyl)-7-(1(1,3-dicarboxypropyl))-1,4,7,10-tetraaza-cyclododec-1-yl]acetyl]-Tyr(3)-octreotate (DOTA-t-GA-tate) were radio-labeled with (111)In or (88)Y and their biodistribution profiles together with their elimination characteristics in rats were compared.

Highly improved metabolic stability and pharmacokinetics of indium-111-DOTA-gastrin conjugates for targeting of the gastrin receptor

The development of metabolically stable radiolabeled gastrin analogues with suitable pharmacokinetics is a topic of recent research activity. These imaging vectors are of interest because the gastrin/CCK2 receptor is highly overexpressed in different tumors such as medullary thyroid cancer, neuroendocrine tumors, and SCLC. The drawback of current targeting agents is either their metabolic instability or their high kidney uptake. We present the synthesis and in vitro and in vivo evaluation of 11 (111)In-labeled DOTA-conjugated peptides that differ by their spacer between the peptide and the chelate. We introduced uncharged but hydrophilic spacers such as oligoethyleneglycol, serine, and glutamine. The affinity of all radiopeptides was high with IC(50) values between 0.5 and 4.8 nM. The improvement of human serum stability is 500-fold within this series of compounds. In addition the kidney uptake could be lowered distinctly and the tumor-to-kidney ratio improved almost 60-fold if compared with radiotracers having charged spacers such as glutamic acid.

Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers

Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes.

Evidence for extinct Cs-135 from Ba isotopes in Allende CAIs?

he abundance and distribution of isotopes throughout the Solar System can be used to constrain the number and type of nucleosynthetic events that contributed material to the early nebula. Barium is particularly well suited to quantifying the degree of isotope heterogeneity in the Solar System because it comprises seven stable isotopes that were synthesized by three different nucleosynthetic processes (s-, r-, and p-processes), all of which contributed material to the Solar System. There is also potential contribution to 135Ba from short-lived radioisotope 135Cs, conclusive evidence for which is yet to be reported. Four Allende (CV3) Ca,Al-rich inclusions (CAI 1, CAI 2, CAI 4, CAI 5) and one Allende dark inclusion (DI) were analyzed for Ba isotope variability. Two CAIs (CAI 2 and CAI 5) display 135Ba excesses that are not accompanied by 137Ba anomalies. Calcium–aluminum-rich inclusion 1 displays a 135Ba excess that is possibly coupled with a 137Ba excess, and the remaining refractory inclusions (CAI 2 and DI) have terrestrial Ba isotope compositions. These Ba isotope data are presented in conjunction with published whole rock Ba isotope data from individual Allende CAIs. The enrichment in 135Ba and absence of coupled 137Ba excesses in CAI 2 and CAI 5 is interpreted to indicate that the anomalies are not purely nucleosynthetic in origin but also contain contributions (16–48 ppm) from the decay of short-lived 135Cs. The majority of Allende CAIs studied to date may also have similar contributions from 135Cs on the basis of higher than expected 135Ba excesses if the Ba isotope anomalies were purely nucleosynthetic in origin. The 135Ba anomalies appear not to be coupled with superchondritic Cs/Ba, which may imply that the contribution to 135Ba did not occur via in situ decay of live 135Cs. However, it is feasible that the CAIs had a superchondritic Cs/Ba during decay of 135Cs, but Cs was subsequently removed from the system during aqueous alteration on the parent body. An alternative scenario is the potential existence of a transient high-temperature reservoir having superchondritic Cs/Ba in the early Solar System while 135Cs was extant, which enabled a radiogenic 135Ba signature to develop in some early condensates. The nucleosynthetic source of 135Cs can be determined by reconciling the predicted astrophysical 135Cs abundance with its measured abundance in meteorites. Further, the currently accepted initial 135Cs/133Cs of the Solar System, [135Cs/133Cs]0, may be underestimated because the spread of Cs/Ba among samples is small and the range of excess 135Ba is limited thus leading to inaccuracies when estimating [135Cs/133Cs]0. If the initial meteoritic abundance of 135Cs was indeed higher than is currently thought, the most probable stellar source of short-lived radioisotopes was a nearby core-collapse supernova and/or the Wolf–Rayet wind driven by its progenitor.

Layer-by-layer grown scalable redox-active ruthenium-based molecular multilayer thin films for electrochemical applications and beyond

Here we report the first study on the electrochemical energy storage application of a surface-immobilized ruthenium complex multilayer thin film with anion storage capability. We employed a novel dinuclear ruthenium complex with tetrapodal anchoring groups to build well-ordered redox-active multilayer coatings on an indium tin oxide (ITO) surface using a layer-by-layer self-assembly process. Cyclic voltammetry (CV), UV-Visible (UV-Vis) and Raman spectroscopy showed a linear increase of peak current, absorbance and Raman intensities, respectively with the number of layers. These results indicate the formation of well-ordered multilayers of the ruthenium complex on ITO, which is further supported by the X-ray photoelectron spectroscopy analysis. The thickness of the layers can be controlled with nanometer precision. In particular, the thickest layer studied (65 molecular layers and approx. 120 nm thick) demonstrated fast electrochemical oxidation/reduction, indicating a very low attenuation of the charge transfer within the multilayer. In situ-UV-Vis and resonance Raman spectroscopy results demonstrated the reversible electrochromic/redox behavior of the ruthenium complex multilayered films on ITO with respect to the electrode potential, which is an ideal prerequisite for e.g. smart electrochemical energy storage applications. Galvanostatic charge–discharge experiments demonstrated a pseudocapacitor behavior of the multilayer film with a good specific capacitance of 92.2 F g−1 at a current density of 10 μA cm−2 and an excellent cycling stability. As demonstrated in our prototypical experiments, the fine control of physicochemical properties at nanometer scale, relatively good stability of layers under ambient conditions makes the multilayer coatings of this type an excellent material for e.g. electrochemical energy storage, as interlayers in inverted bulk heterojunction solar cell applications and as functional components in molecular electronics applications.

Towards tailored radiopeptide therapy.

PURPOSE Somatostatin receptor-targeted radiopeptide therapy is commonly performed using single radioisotopes. We evaluated the benefits and harms of combining radioisotopes in radiopeptide therapy in patients with neuroendocrine tumor. METHODS Using multivariable-adjusted survival analyses and competing risk analyses we evaluated outcomes in patients with neuroendocrine tumor receiving (90)Y-DOTATOC, (177)Lu-DOTATOC or their combination. RESULTS (90)Y-DOTATOC plus (177)Lu-DOTATOC treatment was associated with longer survival than (90)Y-DOTATOC (66.1 vs. 47.5 months; n = 1,358; p < 0.001) or (177)Lu-DOTATOC alone (66.1 vs. 45.5 months; n = 390; p < 0.001). (177)Lu-DOTATOC was associated with longer survival than (90)Y-DOTATOC in patients with solitary lesions (HR 0.3, range 0.1 - 0.7; n = 153; p = 0.005), extrahepatic metastases (HR 0.5, range 0.3 - 0.9; n = 256; p = 0.029) and metastases with low uptake (HR 0.1, range 0.05 - 0.4; n = 113; p = 0.001). (90)Y-DOTATOC induced higher hematotoxicity rates than combined treatment (9.5% vs. 4.0%, p = 0.005) or (177)Lu-DOTATOC (9.5 vs. 1.4%, p = 0.002). Renal toxicity was similar among the treatments. CONCLUSIONS Using (90)Y and (177)Lu might facilitate tailoring radiopeptide therapy and improve survival in patients with neuroendocrine tumors.