Synergistic Effect of Metal-Organic Framework/Gallic Acid in Enhanced Laser Desorption/Ionization Mass Spectrometry.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has become an indispensable tool for high-throughput analysis of macromolecules, but many challenges still remain in detection of small molecules due to the severe matrix-related background interference in the low-molecular-weight ranges (MW < 700 Da). Herein, a gallic acid (GA)-functionalized zirconium 1,4-dicarboxybenzene metal-organic framework (MOF) (denoted as UiO-66-GA) was designed to serve as a new substrate, and a novel strategy on the basis of the synergistic effect of MOF and GA was developed to enhance the LDI process. In comparison with conventional organic matrices, the UiO-66-GA substrate showed superior LDI performance in the analysis of a wide variety of molecules including amino acids, unsaturated fatty acids, bisphenols (BPs), oligosaccharides, peptides, protein, and polyethylene glycol (PEG) of various average molecular weights from 200 to 10000. Perfluorooctanoic sulfonate (PFOS) was used to evaluate the ability of quantitative analysis, and its corresponding limit of detection as low as 1 fmol was achieved. High sensitivity and good salt tolerance of the UiO-66-GA-assisted LDI-MS were allowed to determine ultratrace PFOS in the spiked human urine and serum samples. In addition, the synergistic mechanism of MOF and GA in the enhanced LDI process was investigated by comprehensively comparing GA- and its analogue-functionalized UiO-66, and the results revealed that two aspects contributed to the enhanced LDI process: (1) an enhancement in the metal-phenolic coordination system of UiO-66-GA promoted laser absorption and energy transfer; (2) introduction of carboxyl and hydroxyl groups of GA onto UiO-66 facilitated the LDI process in both positive and negative ion modes. This work expands a new domain for the MOF applications and provides a promising alternative for various molecule analyses.

66Ga: A Novelty or a Valuable Preclinical Screening Tool for the Design of Targeted Radiopharmaceuticals?

Emerging interest in extending the plasma half-life of small molecule radioligands warrants a consideration of the appropriate radionuclide for PET imaging at longer time points (>8 h). Among candidate positron-emitting radionuclides, 66Ga (t1/2 = 9.5 h, ß+ = 57%) has suitable nuclear and chemical properties for the labeling and PET imaging of radioligands of this profile. We investigated the value of 66Ga to preclinical screening and the evaluation of albumin-binding PSMA-targeting small molecules. 66Ga was produced by irradiation of a natZn target. 66Ga3+ ions were separated from Zn2+ ions by an optimized UTEVA anion exchange column that retained 99.99987% of Zn2+ ions and allowed 90.2 ± 2.8% recovery of 66Ga3+. Three ligands were radiolabeled in 46.4 ± 20.5%; radiochemical yield and >90% radiochemical purity. Molar activity was 632 ± 380 MBq/µmol. Uptake in the tumor and kidneys at 1, 3, 6, and 24 h p.i. was determined by µPET/CT imaging and more completely predicted the distribution kinetics than uptake of the [68Ga]Ga-labeled ligands did. Although there are multiple challenges to the use of 66Ga for clinical PET imaging, it can be a valuable research tool for ligand screening and preclinical imaging beyond 24 h.

Concurrent spectrometry of annihilation radiation and characteristic gamma-rays for activity assessment of selected positron emitters.

A method is described to determine the activity of non-pure positron emitters in a radionuclide production environment by assessing the 511keV annihilation radiation concurrently with selected γ-lines, using a single High-Purity Germanium (HPGe) detector. Liquid sources of 22Na, 52Fe, 52mMn, 61Cu, 64Cu, 65Zn, 66Ga, 68Ga, 82Rb, 88Y, 89Zr and 132Cs were prepared specifically for this study. Acrylic absorbers surrounding the sources ensured that the emitted ß+-particles could not escape and annihilate away from the source region. The absorber thickness was matched to the maximum ß+ energy for each radionuclide. The effect on the 511keV detection efficiency by the non-homogeneous distribution of annihilation sites inside the source and absorber materials was investigated by means of Monte Carlo simulations. It was found that no self-absorption corrections other than those implicit to the detector calibration procedure needed to be applied. The medically important radionuclide, 64Cu, is of particular interest as its strongest characteristic γ-ray has an intensity of less than 0.5%. In spite of the weakness of its emission intensity, the 1346keV γ-line is shown to be suitable for quantifying the 64Cu production yield after chemical separation from the target matrix has been performed.