Target manufacturing by Spark Plasma Sintering for efficient 89Zr production.

Zirconium-89 (89Zr) is an emerging radionuclide for positron emission tomography (PET), with nuclear properties suitable for imaging slow biological processes in cellular targets. The 89Y(p,n)89Zr nuclear reaction is commonly exploited as the main production route with medical cyclotrons accelerating low-energy (< 20 MeV) and low-current (< 100 µA) proton beams. Usually, natural yttrium solid targets manufactured by different methods, including yttrium electrodeposition, yttrium sputtering, compressed yttrium powders, and foils, were employed. In this study, the Spark Plasma Sintering (SPS) technique has been investigated, for the first time, to manufacture yttrium solid targets for an efficient 89Zr radionuclide yield. The natural yttrium disc was bonded to a niobium backing plate using a commercial SPS apparatus and a prototype machine assembled at the University of Pavia. The resulting targets were irradiated in a TR19 cyclotron with a 12 MeV proton beam at 50 µA. A dedicated dissolution module, obtained from a commercial system, was used to develop an automated process for the purification and recovery of the produced 89Zr radionuclide. The production yield and recovery efficiency were measured and compared to 89Zr produced by irradiating standard yttrium foils. SPS manufactured targets withstand an average heat power density of approximately 650 W∙cm-2 for continuous irradiation up to 5 h without visible damage. A saturation yield of 14.12 ± 0.38 MBq/µAh was measured. The results showed that the obtained 89Zr production yield and quality were comparable to similar data obtained using standard yttrium foil targets. In conclusion, the present work demonstrates that the SPS technique might be a suitable technical manufacturing solution aimed at high-yield 89Zr radioisotope production.

Coalescence of Macroscopic Flux Ropes at the Subsolar Magnetopause: Magnetospheric Multiscale Observations.

We report unambiguous in situ observation of the coalescence of macroscopic flux ropes by the magnetospheric multiscale (MMS) mission. Two coalescing flux ropes with sizes of ∼1 R_{E} were identified at the subsolar magnetopause by the occurrence of an asymmetric quadrupolar signature in the normal component of the magnetic field measured by the MMS spacecraft. An electron diffusion region (EDR) with a width of four local electron inertial lengths was embedded within the merging current sheet. The EDR was characterized by an intense parallel electric field, significant energy dissipation, and suprathermal electrons. Although the electrons were organized by a large guide field, the small observed electron pressure nongyrotropy may be sufficient to support a significant fraction of the parallel electric field within the EDR. Since the flux ropes are observed in the exhaust region, we suggest that secondary EDRs are formed further downstream of the primary reconnection line between the magnetosheath and magnetospheric fields.

Analytical performance of an heterogeneous enzyme immunoassay using the same separation system.

A single "one step" solid phase sandwich enzyme immunoassay was developed. The assay employs two monoclonal antibodies with affinity and specificity for different epitopes of the analyte: one is covalently coupled to peroxidase, while the other one is coupled to biotin. The addition of the reagent to an avidin-coated strip gave a specific and efficient mean for binding the sandwich complex to the solid phase, via the high affinity interaction between biotin and avidin. The methodology was applied to the determination of hypophysis hormones (LH, FSH, PRL), tumor markers (CEA, AFP, FRT, hCG beta free subunit, alpha subunit and others alpha-P Amylase). Analytical performances concerning the developed kits are described, demonstrating the good reproducibility, sensitivity, accuracy and the wide application field for this new technology.

Rapid potentiometric determination of cholinesterases in plasma and red cells: application to eptastigmine monitoring.

Eptastigmine (MF 201) is a new physostigmine derivative with potent inhibitory activity on cholinesterases. Here we present a new potentiometric cholinesterase activity assay suitable for MF 201 monitoring. The analysis is performed on a differential pH system and has the following characteristics: (a) within-run precision: C.V. 2.0% (plasma cholinesterase), 1.8% (red cell cholinesterase); (b) between-run precision: C.V. 4.0% (plasma cholinesterase); (c) linearity: 1-10 kU/l (plasma cholinesterase), 6-70 U/g Hb (red cell cholinesterase); (d) comparison with a reference method (x, HITACHI 737 Boerhinger Mannheim, Italy): y = 0.785x - 0.07; n = 37; r = 0.998. The assay has been applied to the determination of plasma and red cell cholinesterase activity in volunteers over 60 years of age treated with a single oral dose of 30 mg eptastigmine. We found that red cell cholinesterase is selectively inhibited after MF 201 administration with the following kinetics (time, % of inhibition, mean +/- S.E., n = 6): 0 h, 0; 1 h, 17 +/- 4.6; 2 h, 24 +/- 4; 4 h, 23 +/- 4.4; 12 h, 14 +/- 3. Eptastigmine plasma levels were also determined by a HPLC method: maximum concentration was found one hour after drug administration.

Whole blood L-lactate assay by a new differential pH method: application to metabolic investigations.

We propose a new quantitative method for L-lactate assay in whole blood, based on the measurement of pH variation caused by specific and irreversible oxidation of L-lactate to pyruvate in the presence of an electron acceptor (hexacyanoferrate) and of the enzyme cytochrome b2 (EC 1.1.2.3.). No sample pretreatment is needed; the method is simple and fast (1.5 min/analysis) and requires 10 microliters whole blood per assay. Linearity is confirmed up to 20 mmol/l L-lactate. Within-day and between-day variability was (as C.V.) 3.6% and 8.1% for blood lactate 1.3 and 1.0 mmol/l, respectively. The results by the present method correlate well with those from two reference methods (test method vs a lactate sensor based method: r = 0.996; test method vs a spectrophotometric method: r = 0.987). An application of the present method to the continuous monitoring of L-lactate in patients after combined kidney and pancreas transplantation, under conditions of euglycemic hyperinsulinemia and hyperglycemic hyperinsulinemia is reported. We conclude that the method is simple and reproducible and can be employed to measure whole blood lactate concentration continuously both in clinical protocols and in basic research.