Preparation and biodistribution of [67Ga]-DTPA-rituximab in normal rats

Rituximab was successively labeled with [⁶⁷Ga]-gallium chloride after residulation with freshly prepared cyclic DTPA-dianhydride. The best results of the conjugation were obtained by the addition of 1 ml of a rituximab pharmaceutical solution (5 mg/ml, in phosphate buffer, pH 8) to a glass tube pre-coated with DTPA-dianhydride (0.01 mg) at 25 °C with continuous mild stirring for 30 minutes. Radio thin-layer chromatography showed an overall radiochemical purity of 96–99% at optimized conditions (specific activity = 300–500 MBq/mg, labeling efficiency 77%). The final isotonic ⁶⁷Ga-DTPA-rituximab complex was checked by gel electrophoresis for radiolysis control. Radio-TLC was performed to ensure the formation of only one species, followed by filtration through a 0.22 μm filter. Preliminary in vivo studies in normal rat model was performed to determine the biodistribution of the radioimmunoconjugate up to 6 hours.     

Hybrid phospholipid bilayer coatings for separations of cationic proteins in capillary zone electrophoresis

Protein separations in CZE suffer from nonspecific adsorption of analytes to the capillary surface. Semipermanent phospholipid bilayers have been used to minimize adsorption, but must be regenerated regularly to ensure reproducibility. We investigated the formation, characterization, and use of hybrid phospholipid bilayers (HPBs) as more stable biosurfactant capillary coatings for CZE protein separations. HPBs are formed by covalently modifying a support with a hydrophobic monolayer onto which a self‐assembled lipid monolayer is deposited. Monolayers prepared in capillaries using 3‐cyanopropyldimethylchlorosilane (CPDCS) or n‐octyldimethylchlorosilane (ODCS) yielded hydrophobic surfaces with lowered surface free energies of 6.0 ± 0.3 or 0.2 ± 0.1 mJ m^?2, respectively, compared to 17 ± 1 mJ m^?2 for bare silica capillaries. HPBs were formed by subsequently fusing vesicles comprised of 1,2‐dilauroyl‐sn‐glycero‐3‐phosphocholine or 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine to CPDCS‐ or ODCS‐modified capillaries. The resultant HPB coatings shielded the capillary surface and yielded reduced electroosmotic mobility (1.3–1.9 × 10^?4 cm² V^?1s^?1) compared to CPDCS‐ and ODCS‐modified or bare capillaries (3.6 ± 0.2 × 10^?4 cm² V^?1s^?1, 4.8 ± 0.4 × 10^?4 cm² V^?1s^?1, and 6.0 ± 0.2 × 10^?4 cm² V^?1s^?1, respectively), with increased stability compared to phospholipid bilayer coatings. HPB‐coated capillaries yielded reproducible protein migration times (RSD ≤ 3.6%, n ≥ 6) with separation efficiencies as high as 200 000 plates/m.     

A General Optimality Conditions for Stochastic Control Problems of Jump Diffusions

We consider a stochastic control problem where the system is governed by a non linear stochastic differential equation with jumps. The control is allowed to enter into both diffusion and jump terms. By only using the first order expansion and the associated adjoint equation, we establish necessary as well as sufficient optimality conditions of controls for relaxed controls, who are a measure-valued processes.     

Practical considerations for preparing polymerized phospholipid bilayer capillary coatings for protein separations

Phosphorylcholine (PC) based phospholipid bilayers have proven useful as capillary coating materials due to their inherent resistance to non-specific protein adsorption. The primary limitation of this important class of capillary coatings remains the limited long-term chemical and physical stability of the coatings. Recently, a method for increasing phospholipid coating stability in fused silica capillaries via utilization of polymerized, synthetic phospholipids was reported. Here, we expand upon these studies by investigating polymerized lipid bilayer capillary coatings with respect to separation performance including run-to-run, day-to-day and column-to-column reproducibility and long-term stability. In addition, the effects of pH and capillary inner diameter on polymerized phospholipid coated capillaries were investigated to identify optimized coating conditions. The coatings are stabilized for protein separations across a wide range of pH values (4.0–9.3), a unique property for capillary coating materials. Additionally, smaller inner diameter capillaries (≤50 μm) were found to yield marked enhancements in coating stability and reproducibility compared to wider bore capillaries, demonstrating the importance of capillary size for separations employing polymerized phospholipid coatings.     

Exact solutions to the space–time fractional Schrödinger–Hirota equation and the space–time modified KDV–Zakharov–Kuznetsov equation

In this paper, the first integral method and the functional variable method are used to establish exact traveling wave solutions of the space–time fractional Schrödinger–Hirota equation and the space–time fractional modified KDV–Zakharov–Kuznetsov equation in the sense of conformable fractional derivative. The results obtained confirm that proposed methods are efficient techniques for analytic treatment of a wide variety of the space–time fractional partial differential equations.     

Development of [<Superscript>64</Superscript>Cu]-DOTA-anti-CD20 for targeted therapy

Copper-64 was produced as a by-product of ⁵⁵Co via ⁶⁴Ni(p,n)⁶⁴Cu by 15 MeV proton bombardment of ^natNi resulting in a thick target yield of 5.31 MBq/μAh (143.5 μCi/μAh) and a radiochemical separation yield of 95% (radionuclide purity >97% after 25 hours of bombardment). Rituximab was successively labeled with [⁶⁴Cu]-CuCl₂. N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 °C using DOTA and N-hydroxy succinimide (NHS) in CH₂Cl₂ followed by the addition of 1 ml of a Rituximab pharmaceutical solution. Radiolabeling was performed at 37 °C in 3 hours. Radio thin-layer chromatography showed an overall radiochemical purity of 90–95% at optimized conditions (specific activity=30 GBq/mg, labeling efficacy; 82%) using various chromatography systems. The final isotonic ⁶⁴Cu-DOTA-Rituximab complex was passed through a 0.22 μm filter and checked by gel electrophoresis for radiolysis control. Stability of the final product was checked in the formulation and in presence of human serum at 37 °C.     

On-column N-dearylation of 2-azetidinones by silica-supported ceric ammonium nitrate

A modified traditional preparative chromatographic column can be used to achieve quantitative N-dearylation of N-(alkoxyphenyl), N-(alkoxynaphthyl), and N-(alkoxybenzyl)-2-azetidinones under mild conditions. Starting materials are charged on top of the column and the pure N-unsubstituted 2-azetidinones leave the column minutes later without need for other purifications. The yields are good-to-excellent and the reaction condition is mild, easy, efficient, and cheap.     

Fourth body gravitation effect on the resonance orbit characteristics of the restricted three-body problem

In this paper, the gravitational effect of a fourth body on the resonance orbit defined in the restricted three-body problem (RTBP) is considered. In this regard, Resonance Hamiltonian of the RTBP and the Hamiltonian associated with the fourth gravitational body that perturbs the resonance orbit are computed. The Melnikov approach is utilized as a mean for the detection of chaos in resonance orbit under the influence of the fourth gravitation body. In addition, the numerical simulation of RTBP and bicircular four-body model, time–frequency analysis (TFA), and fast Lyapunov indicator (FLI) are performed to verify the results of the Melnikov approach. The results indicate that for the (2:1) resonance orbit, the Melnikov integral computed over outer loop of separatrix does not cross the zero line, and consequently chaos is unexpected. On the other hand, the Melnikov integral computed over the inner sepratrix loop crosses the zero line indicating a potential for chaos. Similarly, it is shown that inclusion of the fourth body gravitation leads the (3:1) as well as the (4:1) resonance orbits to chaos. Additionally, simulation results indicate that for some initial conditions on the separatrix, the fourth body effect bounds the amplitude of the resonance orbits while diffusing its corresponding trajectory in the bounded phase space. TFA and the FLI verify similar results.