Nanoparticles have been proposed for several biomedical applications due to their potential as drug carriers, diagnostic and therapeutic agents. However, only a few of them have been approved for their use in humans. In order to gauge the potential applicability of a specific type of nanoparticle, in vivo biodistribution studies to characterize their pharmacokinetic properties are essential. In this regard, mesoporous silica nanoparticles (30–130 nm) have been functionalized with amino groups in order to react with N-succinimidyl 4-[18F]fluorobenzoate and thus anchor the 18F positron emission isotope by using a novel and easy labelling strategy. In vivo biodistribution was characterized in mice after intravenous administration of radiolabelled nanoparticles by positron emission tomography. Our results indicated that radiolabelled mesoporous silica nanoparticles were excreted into bile and urine and accumulated mainly in the organs of the reticuloendothelial system and lungs.

Inhaled radioactive CO is currently the tracer of choice for blood volume quantification by positron emission tomography (PET). This measurement is of great interest for several clinical and research applications. However, owing to the short half-life of the radiolabeled CO, it can only be used in centers equipped with a cyclotron. In the present work, we propose an alternative method to label the red blood cells with [(18) F] in order to obtain blood volume measurements by PET. The use of the radioactive synthon [(18) F] N-succinimidyl 4-[(18) F]fluorobenzoate ([(18) F]SFB) was evaluated for erythrocyte labeling and PET blood volume imaging. The images provided by [(18) F]SFB labeled erythrocytes were compared with those obtained with inhaled [(11) C]CO. Blood volumes obtained with [(18) F]SFB labeled erythrocytes were similar to those obtained with [(11) C]CO in all of the evaluated organs with the exception of spleen, which presented lower uptake with this method. Since the [(18) F]-SFB binds irreversibly to red blood cells, in vivo stability of the radiolabel was higher compared with the [(11) C]CO method. Additionally, owing to the longer half-life and the shorter positron range of [(18) F], the image quality was also higher with the [(18) F]SFB radiolabeled erythrocytes. The labeling of red blood with [(18) F]SFB represents an advantageous alternative to radioactive CO for blood volume measurement by PET and cardiovascular isotopic imaging.

A rapid and high-yielding cysteine labelling of peptides has been observed with the specific labelling agent for amines, N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB). Interestingly, conjugation of the 4-fluorobenzoyl (FB) moiety is selectively achieved through a cysteine (Cys) thiol of the peptides with high yield (>80%) in short time (<5 min), while for a Cys amino acid derivative, a slow process has been observed. The large reactivity of these peptides for the conjugation reaction is rationalised on the basis of electrostatic interactions between the sulfhydril and the guanidinium groups of the amino acid side chains. Moreover, the stability of these novel conjugates and the biodistribution of the radiolabelled dodecapeptide by positron emission tomography (PET) in rats has been examined.

Positron emission tomography (PET) has been used extensively to evaluate the neuropathology of Alzheimer's disease (AD) in vivo. Radiotracers directed toward the amyloid deposition such as [18F]-FDDNP (2-(1-{6-[(2-[F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile) and [11C]-PIB (Pittsburg compound B) have shown exceptional value in animal models and AD patients. Previously, the glucose analogue [18F]-FDG (2-[(18)F]fluorodeoxyglucose) allowed researchers and clinicians to evaluate the brain glucose consumption and proved its utility for the early diagnosis and the monitoring of the progression of AD. Animal models of AD are based on the transgenic expression of different human mutant genes linked to familial AD. The novel transgenic 5XFAD mouse containing 5 mutated genes in its genome has been proposed as an AD model with rapid and massive cerebral amyloid deposition. PET studies performed with animal-dedicated scanners indicate that PET with amyloid-targeted radiotracers can detect the pathological amyloid deposition in transgenic mice and rats. However, in other studies no differences were found between transgenic mice and their wild type littermates. We sought to investigate in 5XFAD mice if the radiotracers [11C]-PIB, and [18F]-Florbetapir could quantify the amyloid deposition in vivo and if [18F]-FDG could do so with regard to glucose consumption. We found that 5XFAD animals presented higher cerebral binding of [18F]-Florbetapir, [11C]-PIB, and [18F]-FDG. These results support the use of amyloid PET radiotracers for the evaluation of AD animal models. Probably, the increased uptake observed with [18F]-FDG is a consequence of glial activation that occurs in 5XFAD mice.

Fast cysteine labelling of peptides promoted by an adjacent arginine has been observed with a standard labelling agent specific for amines, N-succinimidyl 4-[(18)F]fluorobenzoate.

A variety of nanoparticles have been proposed for several biomedical applications. To gauge the therapeutic potential of these nanoparticles, in vivo biodistribution is essential and mandatory. In the present study, ceria nanoparticles (5 nm average particle size) were labeled with (18)F to study their in vivo biodistribution in rats by positron emission tomography (PET). The (18)F isotope was anchored by reaction of N-succinimidyl 4-[(18)F]fluorobenzoate ((18)F-SFB) with a modified nanoparticle surface obtained by silylation with 3-aminopropylsilyl. Radiolabeled ceria nanoparticles accumulated mainly in lungs, spleen, and liver. Metabolic products of the radiolabeled nanoparticulate material were excreted into the urinary tract.

Nanoparticles have been proposed for several biomedical applications; however, in vivo biodistribution studies to confirm their potential are scarce. Nanodiamonds are carbon nanoparticles that have been recently proposed as a promising biomaterial. In this study, we labeled nanodiamonds with (18)F to study their in vivo biodistribution by positron emission tomography. Moreover, the impact on the biodistribution of their kinetic particle size and of the surfactant agents has been evaluated. Radiolabeled diamond nanoparticles accumulated mainly in the lung, spleen, and liver and were excreted into the urinary tract. The addition of surfactant agents did not lead to significant changes in this pattern, with the exception of a slight reduction in the urinary excretion rate. On the other hand, after filtration of the radiolabeled diamond nanoparticles to remove those with a larger kinetic size, the uptake in the lung and spleen was completely inhibited and significantly reduced in the liver.

In this study, we assessed the feasibility of using positron emission tomography (PET) and the tracer [11C]OMAR ([11C]JHU75528), an analogue of rimonabant, to study the brain cannabinoid type 1 (CB1) receptor system. Wild-type (WT) andCB1 knockout (KO) animals were imaged at baseline and after pretreatment with blocking doses of rimonabant. Brain uptake in WT animals was higher (50%) than in KO animals in baseline conditions. After pretreatment with rimonabant, WT uptake lowered to the level of KO animals. The results of this study support the feasibility of using PET with the radiotracer [11C]JHU75528 to image the brain CB1 receptor system in mice. In addition, this methodology can be used to assess the effect of new drugs in preclinical studies using genetically manipulated animals.

In this study, we assessed the feasibility of using positron emission tomography (PET) and the tracer [ 11 C]OMAR ([ 11 C]JHU75528), an analogue of rimonabant, to study the brain cannabinoid type 1 (CB1) receptor system. Wild-type (WT) andCB1 knockout (KO) animals were imaged at baseline and after pretreatment with blocking doses of rimonabant. Brain uptake in WT animals was higher (50%) than in KO animals in baseline conditions. After pretreatment with rimonabant, WT uptake lowered to the level of KO animals. The results of this study support the feasibility of using PET with the radiotracer [ 11 C]JHU75528 to image the brain CB1 receptor system in mice. In addition, this methodology can be used to assess the effect of new drugs in preclinical studies using genetically manipulated animals.

Whereas molecular imaging studies in the aging human brain have predominantly demonstrated reductions in serotonin transporter (5-HTT) availability, the majority of the rodent studies, using autoradiographic methods, report increases in neural 5-HTT levels with age. To our knowledge, however, no previous rodent studies have assessed this topic in vivo, and therefore it remains unclear whether this discrepancy arises from methodological or inter-species differences. We performed an [11C]-DASB microPET study to evaluate the effects of aging on 5-HTT availability in the rat brain. To generate binding potential estimates, quantitative tracer kinetic modeling was applied using the simplified reference tissue model. A global increase in whole-brain [11C]-DASB binding potential was observed in the aged rats in comparison to the control group. More specifically, regional analyses revealed a highly significant increase in 5-HTT binding in the medial frontal cortex, and more modest increments in the midbrain/thalamus. Our results suggest that the frontal cortex represents a site of robust age-related alterations in the rat serotonergic system, and stress the need for further research assessing this topic in the human frontal cortex. Moreover, these findings suggest that the reported discrepancies between rodent and human data may reflect a divergence in the aging processes affecting human and rat serotonergic terminals.

The GABA-ergic system, known to regulate neural tissue genesis during cortical development, has been postulated to play a role in cerebral aging processes. Using in vivo molecular imaging and voxel-wise quantification, we aimed to assess the effects of aging on the benzodiazepine (BDZ) recognition site of the GABA(A) receptor. To visualize BDZ site availability, [(11)C]-flumazenil microPET acquisitions were conducted in young and old rats. The data were analyzed and region of interest analyses were applied to validate the voxel-wise approach. We observed decreased [(11)C]-flumazenil binding in the aged rat brains in comparison with the young control group. More specifically, clusters of reduced radioligand uptake were detected in the bilateral hippocampus, cerebellum, midbrain, and bilateral frontal and parieto-occipital cortex. Our results support the pertinence of voxel-wise quantification in the analysis of microPET data. Moreover, these findings indicate that the aging process involves declines in neural BDZ recognition site availability, proposed to reflect alterations in GABA(A) receptor subunit polypeptide expression.

[18F]Fluoromisonidazole (18F-FMISO) is a nitroimidazole derivative that has been proposed as a positron emission tomography (PET) radiotracer to detect hypoxic tissue in vivo. This compound accumulates in hypoxic but viable tissue and may be a good candidate for evaluating the ischemic penumbra. We evaluated the time course of 18F-FMISO uptake using PET in a rat model of permanent cerebral ischemia and the correlation with histological changes.

Intramolecular excited triplet state interactions in diastereomeric compounds composed of a benzophenone chromophore (ketoprofen) and various hydrogen donor moieties (tetrahydrofuran, isopropylbenzene) have been investigated by laser flash photolysis. The rate constants for hydrogen abstraction by excited triplet benzophenone are in the order of 10(4)-10(5) s(-1), with the highest reactivity for the tetrahydrofuran residue. A remarkable diastereodifferentiation, expressed in the triplet lifetimes of the carbonyl chromophore (e.g., 1.6 versus 2.7 micros), has been found for these compounds. With an alkylaromatic moiety as donor, related effects have been observed, albeit strongly dependent on the length of the spacer. The reactivity trend for the initial hydrogen transfer step is paralleled by the quantum yields of the overall photoreaction. The biradicals, formed via remote hydrogen abstraction, undergo intramolecular recombination to macrocyclic ring systems. The new photoproducts have been isolated and characterized by NMR spectroscopy. The stereochemistry of the macrocycles, which contain up to four asymmetric carbons, has been unambiguously assigned on the basis of single-crystal structures and/or NOE effects. Interestingly, a highly regio- and stereoselective macrocyclization has been found for the ketoprofen-tetrahydrofuran conjugates, where hydrogen abstraction from the less substituted carbon is exclusive; cisoid ring junction is always preferred over the transoid junction. The photoreaction is less regioselective for compounds with an isopropylbenzene residue. The reactivity and selectivity trends have been rationalized by DFT (B3LYP/6-31G*) calculations.

A simple set of five components was used to design molecular logic gates based on phthalimide-sensitised Tb(III) luminescence, including the first report of an enabled NOR (EnNOR) gate.

Four new bichromophoric naphthalene dyads in form of diastereomeric pairs are synthesized and photophysically characterized. For a closely related group of compounds (NAP-NAP, MNAP-NAP, MNAP-MNAP), systematic variation of the urea linker led to the observation of intramolecular fluorescence quenching for tertiary urea, but not for secondary urea. Chiral information contained in the dyads has an impact on the efficiency of this process. Furthermore, for the case of (R,R)-MNAP-MNAP, excimer formation in the pre-organized dyad was noted, while being absent in the corresponding (R,S) diastereomer. These differences in photophysical behavior are ascribed to the geometry of the linker and to the chiral information contained in the diastereomeric compounds. Other dyads, such as NPX-NPX, included naproxen as the chromophore. For these compounds strong excimer emission is obtained, however, only very small diastereodifferentiation is observed for the two investigated stereoisomers.

Two dyads containing a naphthalene-like chromophore linked to a pyrrolidine-derived moiety, namely ( S , S )- and ( R , S )-NPX–PYR, have been synthesised by esterification of ( S )- or ( R )-naproxen (NPX) with ( S )- N -methyl-2-pyrrolidinemethanol (PYR) and submitted to photophysical studies (steady-state and time-resolved fluorescence, as well as laser flash photolysis). The emission spectra of the dyads in acetonitrile were characterised by a typical band centred at 350 nm, identical to that of the reference compound ( S )-NPX. However the intensities were clearly different, revealing a significant intramolecular quenching in the dyads, as well as a remarkable stereodifferentiation (factor of 1.6). Accordingly, the fluorescence lifetimes of the two dyads were different from each other and markedly shorter than that of ( S )-NPX. The quenching mechanism is intramolecular electron transfer, that is thermodynamically favoured. Exciplex formation, that is nearly thermoneutral, does not compete efficiently. The electron transfer rate constants for ( S , S )- and ( R , S )-(NPX–PYR) were 1.8 × 10 8 and 2.8 × 10 8 s −1 , respectively. By contrast, no significant intramolecular quenching was observed for the excited triplet states ( λ max = 440 nm), generated by laser flash photolysis; this is in agreement with the fact that intramolecular electron transfer is thermodynamically disfavoured, due to the lower energy of excited triplets.

In the present contribution, wavelength has been used as a tunable parameter to achieve selective control of the photophysics of two novel asymmetric bichromophoric dyads composed of naphthalene units, i.e., 6-methoxynaphthalene (NPX) and 1-methylnaphthalene (NAP) derivatives, with different electronic properties, connected by an amide spacer [(S,S) and (S,R)-NPX-NAP]. As model systems, relevant monochromophoric compounds (NPX-M and NAP-M) have also been investigated. While upon excitation at 325 nm the light energy remained in the NPX moiety, at 290 nm an efficient singlet-singlet energy transfer (phi(SSET) of about 97%) from the NAP unit to the NPX chromophore dominated. A remarkable stereodifferentiation was observed in the excited-state quenching by triethylamine via exciplex formation. The results demonstrate that it is possible to control configuration-dependent interactions in the excited state by wavelength tuning. This can be rationalized through intramolecular interactions of pi systems leading to modulation of the redox properties.

[reaction: see text] Three novel bichromophoric dyads containing dansylamide and 1,8-naphthalimide linked by oligomethylene spacers of varying length were prepared. The fluorescent moiety can be reversibly selected by protonation/deprotonation of the dansyl residue via control of singlet-singlet energy transfer and photoinduced electron transfer, leading to a molecular optical switch with two spectrally distinguished "on" states.

A novel molecular logic gate with inhibit (INH) function has been developed, based on oxygen and a threshold europium concentration as input information and long-lived red europium luminescence as output signal.

Photoinduzierte Wasserstoff-Abspaltungen verlaufen in Diastereomeren aus (S)-Ketoprofen- und (S)- oder (R)-Tetrahydrofurfurylamin-Einheiten mit unterschiedlicher Geschwindigkeit. Zeitaufgelöste Analyse des Keton-Triplettzustands bestätigt das: Die unimolekulare Geschwindigkeitskonstante (kH=3.0×105 s−1) für das S,S-Diastereomer ist viermal so groß wie die für das S,R-Diastereomer (kH=7.5×104 s−1).