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Abstract: The use of a polymeric solid support loaded with a long alkyl chain quaternary ammonium allows the rapid and efficient recovery of cyclotron produced [18F]F− from [18O]water to a low water content organic solution compatible with fast nucleophilic labelling of most precursors for PET radiopharmaceuticals in high yield. [Copyright &y& Elsevier]

Injection of recombinant tissue plasminogen activator (rt-PA) is the standard drug treatment for thrombolysis. However, rt-PA shows risk of hemorrhages and limited efficiency even at high doses. Polysaccharide-poly(isobutylcyanoacrylate) nanoparticles functionalized with fucoidan and loaded with rt-PA were designed to accumulate on the thrombus. Fucoidan has a nanomolar affinity for the P-selectin expressed by activated platelets in the thrombus. Solid spherical fluorescent nanoparticles with a hydrodynamic diameter of 136 ± 4 nm were synthesized by redox radical emulsion polymerization. The clinical rt-PA formulation was successfully loaded by adsorption on aminated nanoparticles and able to be released in vitro . We validated the in vitro fibrinolytic activity and binding under flow to both recombinant P-selectin and activated platelet aggregates. The thrombolysis efficiency was demonstrated in a mouse model of venous thrombosis by monitoring the platelet density with intravital microscopy. This study supports the hypothesis that fucoidan-nanoparticles improve the rt-PA efficiency. This work establishes the proof-of-concept of fucoidan-based carriers for targeted thrombolysis. [ABSTRACT FROM AUTHOR]

Abstract: Radio-HPLC is an essential method to assess the purity of PET radiopharmaceuticals. The usual NaI scintillator radiodetector requires heavy, costly and cumbersome lead shielding. The luminescence LB 500 fLumo detector has been developed to tackle these drawbacks and achieve high sensitivity. The fLumo uses a photon counting detector combined with a flow-through cell modified with a solid melt-on scintillator only sensitive to the positron. This study demonstrates the usefulness of the fLumo for analysis and purification of PET radiopharmaceuticals. [Copyright &y& Elsevier]

Abstract: A fast and reliable method suitable for the automated preparation of (substituted) [18F]fluorobenzyl halides from several [18F]fluorobenzaldehydes was developed. Aromatic nucleophilic substitution of trimethylammonium benzaldehyde triflate and nitro precursors was realized with no-carrier-added [18F]fluoride. After labeling, fluorine-18 containing aldehydes were trapped on a Solid Phase Extraction (SPE) cartridge and the subsequent conversion into benzyl halide was directly realized, on-line, on the support. Reduction of the aldehydes (>95%) was near-quantitative with an aqueous solution of NaBH4. Halogenation was performed on the same support with different aqueous solutions of concentrated acid (HI, HBr, HCl). The conversion of benzyl alcohols into [18F]fluorobenzyl halides (X=Cl, Br, I) usually proceeded within 2min at high yields. The halogenation proceeded at room temperature, with the exception of the 2-[18F]fluoro-3-methoxybenzyl, 2- and 4-[18F]fluorobenzyl halides, which required the use of HBr/HOAc (33%). With this method, various [18F]fluorobenzyl chloride, bromide and iodide compounds were obtained with high radiochemical purities (>90%) and with overall radiochemical yields of 15–70%. The radiosynthesis was completed in 30 or 45min from EOB, starting from the ammonium or nitro precursor, respectively. By using the same solid support, 2- and 4-[18F]fluorobenzyl bromide and iodide derivatives were near-quantitatively converted (>95%) into the corresponding azido compounds (60°C, 5min). As the reduction and halogenation steps were performed on solid supports, automation of the whole synthesis was straightforward. [Copyright &y& Elsevier]

Abstract: Two new silicon-based prosthetic groups, derived from 3-[ethoxybis(1-methylethyl)silyl]propanamine, have been prepared in good yields. These silicon groups bearing an acid or an azide group were coupled to a model tripeptide (Leu-Gly-Gly) either through a classical amide bond formation or through “click chemistry” via the Huisgen cycloaddition. The radiolabelling with fluorine-18 by substitution of the ethoxy group at silicon has been carried out with success in 51–54% decay corrected radiochemical yields. Radiolabelled peptides were easily prepared by direct 18F-fluorination of the silicon-bearing tripeptide or by coupling the peptide with a radiolabelled silicon-based prosthetic group. Their stabilities in physiological medium were studied and proved poor. [Copyright &y& Elsevier]

Using positron emission tomography (PET) and regional cerebral blood flow (rCBF) measurements, we investigated the cerebral correlates of consciousness in a sequence learning task through a novel application of the Process Dissociation Procedure, a behavioral paradigm that makes it possible to separately assess conscious and unconscious contributions to performance. Results show that the metabolic response in the anterior cingulate/mesial prefrontal cortex (ACC/MPFC) is exclusively and specifically correlated with the explicit component of performance during recollection of a learned sequence. This suggests a significant role for the ACC/MPFC in the explicit processing of sequential material. [Copyright &y& Elsevier]