Immunomodulatory effects of targeted radionuclide therapy.

It is now clear that conventional radiation therapy can reinstate cell death immunogenicity. Recent preclinical data indicate that targeted radionuclide therapy that irradiate tumors at continuous low dose rate also can elicit immunostimulatory effects and represents a promising strategy to circumvent immune checkpoint inhibitor resistance. In this perspective, we discuss the accumulating preclinical and clinical data suggesting that activation of the immune system through the cGAS-STING axis and the release of extracellular vesicles by irradiated cells, participate to this antitumor immunity. This should need to be considered for adapting clinical practices to state of the art of the radiobiology and to increase targeted radionuclide therapy effectiveness.

Near-Edge X-ray Absorption Fine Structure Investigation of the Quasi-One-Dimensional Organic Conductor (TMTSF)2PF6.

We present high-resolution near-edge X-ray absorption fine structure (NEXAFS) measurements at the P L2/3 edges, F K edge, C K edge, and Se M2/3 edges of the quasi-one-dimensional (1D) conductor and superconductor (TMTSF)2PF6. NEXAFS allows probing the donor and acceptor moieties separately; spectra were recorded between room temperature (RT) and 30 K at normal incidence. Spectra taken around RT were also studied as a function of the angle (θ) between the electric field of the X-ray beam and the 1D conducting direction. In contrast with a previous study of the S L2/3-edges spectra in (TMTTF)2AsF6, the Se M2/3 edges of (TMTSF)2PF6 do not exhibit a well-resolved spectrum. Surprisingly, the C K-edge spectra contain three well-defined peaks exhibiting strong and nontrivial θ and temperature dependence. The nature of these peaks as well as those of the F K-edge spectra could be rationalized on the basis of first-principles DFT calculations. Despite the structural similarity, the NEXAFS spectra of (TMTSF)2PF6 and (TMTTF)2AsF6 exhibit important differences. In contrast with the case of (TMTTF)2AsF6, the F K-edge spectra of (TMTSF)2PF6 do not change with temperature despite stronger donor-anion interactions. All these features reveal subtle differences in the electronic structure of the TMTSF and TMTTF families of salts.

Donor-anion interactions at the charge localization and charge ordering transitions of (TMTTF)2AsF6 probed by NEXAFS.

High-resolution near-edge X-ray absorption fine structure (NEXAFS) measurements at the As M-edge, F K-edge and S L-edge of the Fabre salt (TMTTF)2AsF6 were performed from room temperature (RT) to 90 K, allowing to reach the charge localization regime below Tρ ≈ 230 K and to cross the charge ordering (CO) transition at TCO ≈ 102 K. The F K-edge and S L-edge spectra exhibit several transitions which have been indexed on the basis of first-principles DFT calculations. Upon cooling from RT significant energy shifts up to +0.8 eV and -0.4 eV were observed in transitions exhibited by the F 1s and S 2p spectra respectively, while the As 3p doublet does not show a significant shift. Opposite energy shifts found in the F 1s and S 2p spectra reflect substantial thermal changes in the electronic environment of F atoms of the anion and S atoms of TMTTF. The changes found around the charge localization crossover suggest an increase of the participation of the S d orbitals in the empty states of TMTTF as well as an increase of the strength of donoranion interactions. A new F 1s pre-edge signal detected upon entry into the CO phase is a clear fingerprint of the symmetry breaking occurring at TCO. We propose that this new transition is caused by a substantial mixing between the HOMO of the AsF6(-) anion and the unoccupied part of the TMTTF HOMO conduction band. Analysis of the whole spectra also suggests that the loss of the inversion symmetry associated with the CO is due to an anion displacement increasing the strength of SF interactions. Our data show unambiguously that anions are not, as previously assumed, innocent spectators during the electronic modifications experienced by the Fabre salts upon cooling. In particular the interpretation of the spectra pointing out a thermally dependent mixing of anion wave functions with those of the TMTTF chains demonstrates for the first time the importance of anion-donor interactions.

²°¹Tl⁺-labelled Prussian blue nanoparticles as contrast agents for SPECT scintigraphy.

Prussian blue (PB) and its analogues on the nanometric scale are exciting nano-objects that combine the advantages of molecular-based materials and nanochemistry. Herein, we demonstrate that ultra-small PB nanoparticles of 2-3 nm can be easily labelled with radioactive (201)Tl(+) to obtain new nanoprobes as radiotracers for 201-thallium-based imaging.

Inhomogeneous superconductivity in organic conductors: the role of disorder and magnetic field.

Several experimental studies have shown the presence of spatially inhomogeneous phase coexistence of superconducting and non-superconducting domains in low dimensional organic superconductors. The superconducting properties of these systems are found to be strongly dependent on the amount of disorder introduced in the sample regardless of its origin. The suppression of the superconducting transition temperature T(c) shows a clear discrepancy with the result expected from the Abrikosov-Gor'kov law giving the behavior of T(c) with impurities. On the basis of the time dependent Ginzburg-Landau theory, we derive a model to account for this striking feature of T(c) in organic superconductors for different types of disorder by considering the segregated texture of the system. We show that the calculated T(c) quantitatively agrees with experiments. We also focus on the effect of superconducting fluctuations on the upper critical fields H(c2) of layered superconductors showing slab structure where superconducting domains are sandwiched by non-superconducting regions. We found that H(c2) may be strongly enhanced by such fluctuations.

Ground state of the quasi-1D compound BaVS3 resolved by resonant magnetic x-ray scattering.

Resonant magnetic x-ray scattering near the vanadium L2,3-absorption edges has been used to investigate the low temperature magnetic structure of high quality BaVS3 single crystals. Below T(N)=31 K, the strong resonance revealed a triple-incommensurate magnetic ordering at the wave vector (0.226   0.226   ξ) in hexagonal notation, with ξ=0.033. The azimuthal-angle dependence of the scattering signal and time-dependent density functional theory simulations indicate an antiferromagnetic order within the ab plane with the spins polarized along a in the monoclinic structure.

Evidence for lattice effects at the charge-ordering transition in (TMTTF)2X.

High-resolution thermal expansion measurements have been performed for exploring the mysterious "structureless transition" in (TMTTF)2X (X=PF(6) and AsF6), where charge ordering at T(CO) coincides with the onset of ferroelectric order. Particularly distinct lattice effects are found at T(CO) in the uniaxial expansivity along the interstack c direction. We propose a scheme involving a charge modulation along the TMTTF stacks and its coupling to displacements of the counteranions X-. These anion shifts, which lift the inversion symmetry enabling ferroelectric order to develop, determine the 3D charge pattern without ambiguity. Evidence is found for another anomaly for both materials at T(int) approximately 0.6T(CO) indicative of a phase transition related to the charge ordering.

PCC-FISH in skin fibroblasts for local dose assessment: biodosimetric analysis of a victim of the Georgian radiological accident.

We propose a new method of biodosimetry that could be applied in cases of localized irradiation. The approach is based on excess chromosome segments determination by the PCC-FISH technique in fibroblasts isolated from skin biopsy. Typically, 0 to 10 Gy ex vivo gamma-irradiated human skin biopsies were dissociated and fibroblasts were isolated and grown for several days. Cells next underwent PCC-FISH painting of whole chromosome 4, and the number of excess chromosome segments per metaphase was determined. An ex vivo reference curve correlating the number of excess chromosome segments per metaphase to the radiation dose was established and used to assess the dose delivered to the skin of one of the victims of the radiological accident that occurred at Lia in Georgia in December 2001. Specifically, the victim suffering from moist desquamation underwent skin excision in Hospital Percy (France). Measurement of excess chromosome segments per metaphase was done in fibroblasts isolated and grown from removed wounded skin and subsequent conversion to radiation doses was performed. The radiation dose map obtained was shown to be in accordance with clinical data and physical dosimetry as well as with conventional biodosimetry. These results demonstrated that PCC-FISH painting applied to skin fibroblasts may be a suitable technique for dose estimation. To assess its worth, this approach needs to be extended to future accidents involving localized radiation exposure.

Formation of modified DNA bases in cells exposed either to gamma radiation or to high-LET particles.

The aim of the present study was to measure the formation of eight base modifications in the DNA of cells exposed to either low-LET ((60)Co gamma rays) or high-LET ((12)C(6+) particles) radiation. For this purpose, a recently optimized HPLC-MS/MS method was used subsequent to DNA extraction and hydrolysis. The background level of the measured modified bases and nucleosides was shown to vary between 0.2 and 2 lesions/10(6) bases. Interestingly, thymidine glycols constitute the main radiation-induced base modifications, with an overall yield of 0.097 and 0.062 lesion/10(6) bases per gray for gamma rays and carbon heavy ions, respectively. Both types of radiations generate four other major degradation products, in the following order of decreasing importance: FapyGua > 5-HmdUrd > 5-FordUrd > 8-oxodGuo. The yields of formation of FapyAde and 8-oxoAde are one order of magnitude lower than those of the related guanine modifications, whereas the radiation-induced generation of 5-OHdUrd was below the limit of detection of the assay. The efficiency for both types of radiation to generate base damage in cellular DNA is low because the highest yield per gray was 0.097 thymine glycols per 10(6) DNA bases. As a striking observation, the yield of formation of the measured DNA lesions was found to be, on average, twofold lower after exposure to high-LET radiation ((12)C(6+)) than after exposure to low-LET gamma radiation. These studies show that the HPLC-MS/MS assay provides an accurate, reliable and sensitive method for measuring cellular DNA base damage.