Quantification of brain cholinergic denervation in Alzheimer's disease using PET imaging with [18F]-FEOBV.

18F-fluoroethoxybenzovesamicol (FEOBV) is a new PET radiotracer that binds to the vesicular acetylcholine transporter. In both animals and healthy humans, FEOBV was found sensitive and reliable to characterize presynaptic cholinergic nerve terminals in the brain. It has been used here for we believe the first time in patients with Alzheimer's disease (AD) to quantify brain cholinergic losses. The sample included 12 participants evenly divided in healthy subjects and patients with AD, all assessed with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) cognitive scales. Every participant underwent three consecutive PET imaging sessions with (1) the FEOBV as a tracer of the cholinergic terminals, (2) the 18F-NAV4694 (NAV) as an amyloid-beta tracer, and (3) the 18F-Fluorodeoxyglucose (FDG) as a brain metabolism agent. Standardized uptake value ratios (SUVRs) were computed for each tracer, and compared between the two groups using voxel wise t-tests. Correlations were also computed between each tracer and the cognitive scales, as well as between FEOBV and the two other radiotracers. Results showed major reductions of FEOBV uptake in multiple cortical areas that were evident in each AD subject, and in the AD group as a whole when compared to the control group. FDG and NAV were also able to distinguish the two groups, but with lower sensitivity than FEOBV. FEOBV uptake values were positively correlated with FDG in numerous cortical areas, and negatively correlated with NAV in some restricted areas. The MMSE and MoCA cognitive scales were found to correlate significantly with FEOBV and with FDG, but not with NAV. We concluded that PET imaging with FEOBV is more sensitive than either FDG or NAV to distinguish AD patients from control subjects, and may be useful to quantify disease severity. FEOBV can be used to assess cholinergic degeneration in human, and may represent an excellent biomarker for AD.

Automated radiosynthesis of N-succinimidyl 3-(di-tert-butyl[(18)F]fluorosilyl)benzoate ([(18)F]SiFB) for peptides and proteins radiolabeling for positron emission tomography.

Recently, silicon fluoride building blocks (SiFA) have emerged as valuable and promising tools to overcome challenges in the labeling of peptides and proteins for positron emission tomography (PET). Herein, we report a fully automated synthesis of N-succinimidyl 3-(di-tert-butyl[(18)F]fluorosilyl)benzoate ([(18)F]SiFB) by a commercially available Scintomics Hot Box 3 synthesis module, to be used as a prosthetic group for peptide and protein labeling. The drying of K2.2.2./K (18)F complex was performed according to the Munich method modified by our group (avoiding azeotropic drying) using oxalic acid to neutralize the base from the (18)F(-) containing QMA eluent. This K2.2.2./K (18)F complex was then used for SiFA (18)F-(19)F isotopic exchange followed by a fast purification by a solid-phase-extraction (SPE) to afford [(18)F]SiFB with an average preparative radiochemical yield (RCY) of 24±1% (non-decay corrected (NDC)) within a synthesis time of 30 min. The [(18)F]SiFB produced by automated synthesis was then used for the (18)F-labeling of rat serum albumin (RSA) as a proof of applicability.

[Decarboxylation of amino acids and peptides in a photoreaction with potassium ferricyanide at 77 K]. / Dekarboksilirovanie aminokislot i peptidov v fotoreaktsii s ferritsianidom kaliia pri 77 K.

We have measured action spectra of formation of radicals in aliphatic amino acids and peptides by reaction of decarboxylation with excited potassium ferricyanide. Peptides are capable to the reaction under longwave absorbtion band excitation, whereas amino acids are stable under these conditions, and decarboxylation occur only under irradiations by lambda < 400 nm.

[Population of triplet-excited states of tryptophanyls and tyrosyls in proteins]. / Zaselennost' tripletno-vozbuzhdennykh sostoianii triptofanilov i tirozilov v belkakh.

The relative limiting concentrations of triplet excited states of tryptophan and tyrosine residues have been measured by the ESR method. The magnitude of limiting concentration of the tryptophan and tyrosine residues T1-states does not vary to fit their numbers in some proteins. A limitation on the concentration of T1-states is accounted for by the fact that in protein molecules there occurs the radiationless excitation energy transfer of chromophores on residues in the triplet state.

[Supernarrow EPR spectrum of aqueous protein solutions, UV-irradiated at 77 K]. / Sverkhuzkii spektr EPR vodnykh rastvorov belkov, UF-obluchennykh pri 77 K.

The nature was studied of paramagnetic centres photoinduced in aqueous solutions of proteins, amino acids and peptides at 77 K, having a supernarrow ESR spectrum with the width 8 mkTl and g = 1.9988 +/- 0.0002. It has been shown that seized electrons localized in deep traps are responsible for this signal. It is suggested that these are metal ions whose nucleus magnetic moment equals zero.

[Phototransformation of radicals appearing in the result of peptide decarboxylation]. / Fotoprevrashchenie radikalov, voznikaiushchikh pri dekarboksilirovanii peptidov.

Photoreactions of peptides Ala-Gly-Gly and Gly-Gly-Gly-Gly in the presence of potassium ferricyanide at 77 K were studied by modeling of ESR spectra. There were obtained parameters of ESR spectra of primary radicals of the peptide glycine residue appearing after decarboxylation, and of the secondary acyl radicals. Dependence of the second integrals of the experimental and triplet and singlet ESR spectra on irradiation time within wave lengths 410-510, 330-390 and greater than 530 nm was measured and discussed.

[Establishment of the site of electron transport chain disruption in mutant Chlamydomonas chloroplasts with an inactive photosystem 2]. / Ustanovlenie mesta narusheniia élektrontransportnoi tsepi khloroplastov mutantov Chlamydomonas s neaktivnoi fotosistemoi 2.

It has been shown in the studies of 6 strains of non-synthesizing Chlamydomonas reinhardi mutants with a damaged electron-transport chain (ETC) in the region of the Photosystem 2 (PS 2) that the damage is localized on the oxidizing side of PS 2. The ESR studies of the mutants have shown that signal 2 is absent in all the mutants, the width of signal 1 in some mutants is lower than in the control, which is, probably, concerned with the differences in the reaction centre structures. The ETC region from electron inlet from the donor--diphenylcarbaside to P700 is capable of functioning. It is suggested that in all the mutants studied the complex responsible for photodissociation of water is damaged.

[Yield of pigment cation-radicals in the reaction of quinone photooxidation of chlorophyll]. / Issledovanis vykhoda kation-radikalov pigments v reaktsii fotookisleniia khlorofilla khinonami

Photoinduced transfer of electrons in alkohol solutions of chlorophyll and its deuterated analog, deuterochlorophyll containing the quinoses: p-benzoquinone, chloranyl, duroquinone, 1,4-naftoquinone and ubiquinone (coenzyme Q6) is studied. It is shown that pigment cation-radical and quinone anion-radical are the primary products of photoreaction. A relationship between stationary concentrations of deuterochlorophyll and p-benzoquinone radicals and quinone concentration in solution is obtained. The reaction mechanism and causes of other authors' (G. Tollin et al.) failure in finding pigment cation-radicals which are formed in the reaction of the latter with quinoses are discussed. It is shown that optimal conditions for accumulating photoinduced cation-radicals of the pigment in pigment solutions of chlorophyll with quinones are lowered temperature, high viscosity of the solvent, low pH of the solution, careful purification of the quinone from hydroquinone admixture.