In vivo biodistribution and tumor uptake of [64Cu]-FAU nanozeolite via positron emission tomography Imaging.

Nanoparticles have emerged as promising theranostic tools for biomedical applications, notably in the treatment of cancers. However, to fully exploit their potential, a thorough understanding of their biodistribution is imperative. In this context, we prepared radioactive [64Cu]-exchanged faujasite nanosized zeolite ([64Cu]-FAU) to conduct positron emission tomography (PET) imaging tracking in preclinical glioblastoma models. In vivo results revealed a rapid and gradual accumulation over time of intravenously injected [64Cu]-FAU zeolite nanocrystals within the brain tumor, while no uptake in the healthy brain was observed. Although a specific tumor targeting was observed in the brain, the kinetics of uptake into tumor tissue was found to be dependent on the glioblastoma model. Indeed, our results showed a rapid uptake in U87-MG model while in U251-MG glioblastoma model tumor uptake was gradual over the time. Interestingly, a [64Cu] activity, decreasing over time, was also observed in organs of elimination such as kidney and liver without showing a difference in activity between both glioblastoma models. Ex vivo analyses confirmed the presence of zeolite nanocrystals in brain tumor with detection of both Si and Al elements originated from them. This radiolabelling strategy, performed for the first time using nanozeolites, enables precise tracking through PET imaging and confirms their accumulation within the glioblastoma. These findings further bolster the potential use of zeolite nanocrystals as valuable theranostic tools.

Physical Activity Attenuates Brain Irradiation-Associated Skeletal Muscle Damage in the Rat.

PURPOSE: Radiation therapy for brain tumors increases patient survival. Nonetheless, side effects are increasingly reported such as cognitive deficits and fatigue. The etiology of fatigue remains poorly described. Our hypothesis is that the abscopal effects of radiation therapy on skeletal muscle may be involved in fatigue. The present study aims to assess the effect of brain irradiation on skeletal muscles and its relationship with fatigue and to analyze whether physical activity could counteract brain radiation-induced side effects. METHODS AND MATERIALS: Adult Wistar rats were randomly distributed between 4 groups: control (CTL), irradiated (IR), nonirradiated with physical activity (PA), and irradiated with physical activity (IR+PA). IR rats were exposed to a whole-brain irradiation (WBI) of 30 Gy (3 × 10 Gy). Rats subjected to PA underwent sessions of running on a treadmill, 3 times/week for 6 months. The effects of WBI on muscles were evaluated by complementary approaches: behavioral tests (fatigue, locomotion activity), magnetic resonance imaging, and histologic analyses. RESULTS: IR rats displayed a significant fatigue and a reduced locomotor activity at short term compared with the CTL group, which were attenuated with PA at 6 months after WBI. The IR rat's gastrocnemius mass decreased compared with CTL rats, which was reversed by physical activity at 14 days after WBI. Multiparametric magnetic resonance imaging of the skeletal muscle highlighted an alteration of the fiber organization in IR rats as demonstrated by a significant decrease of the mean diffusivity in the gastrocnemius at short term. Alteration of fibers was confirmed by histologic analyses: the number of type I fibers was decreased, whereas that of type IIa fibers was increased in IR animals but not in the IR+PA group. CONCLUSIONS: The data show that WBI induces skeletal muscle damage, which is attenuated by PA. This muscle damage may explain, at least in part, the fatigue of patients treated with radiation therapy.

Assessment of hypoxia and oxidative-related changes in a lung-derived brain metastasis model by [64Cu][Cu(ATSM)] PET and proteomic studies.

BACKGROUND: Brain metastases (BM) are the most frequent malignant brain tumors. The aim of this study was to characterize the tumor microenvironment (TME) of BM and particularly hypoxia and redox state, known to play a role in tumor growth and treatment resistance with multimodal PET and MRI imaging, immunohistochemical and proteomic approaches in a human lung cancer (H2030-BrM3)-derived BM model in rats. RESULTS: First, in vitro studies confirmed that H2030-BrM3 cells respond to hypoxia with increasing expression of HIF-1, HIF-2 and their target genes. Proteomic analyses revealed, among expression changes, proteins associated with metabolism, oxidative stress, metal response and hypoxia signaling in particular in cortical BM. [64Cu][Cu(ATSM)] PET revealed a significant uptake by cortical BM (p < 0.01), while no uptake is observed in striatal BM 23 days after tumor implantation. Pimonidazole, HIF-1α, HIF-2α, CA-IX as well as GFAP, CTR1 and DMT1 immunostainings are positive in both BM. CONCLUSION: Overall, [64Cu][Cu(ATSM)] imaging and proteomic results showed the presence of hypoxia and protein expression changes linked to hypoxia and oxidative stress in BM, which are more pronounced in cortical BM compared to striatal BM. Moreover, it emphasized the interest of [64Cu][Cu(ATSM)] PET to characterize TME of BM and depict inter-metastasis heterogeneity that could be useful to guide treatments.

Dating of sediment record at two contrasting sites of the Seine River using radioactivity data and hydrological time series.

Sediment cores were collected at the outlet of the highly anthropogenized catchment of the Seine River at two contrasting sites: a flood plain of the lower Seine River and a quasi-permanently submerged harbour basin (or wet dock) in the upper tidal estuary. Analyses of artificial radionuclides ((137)Cs and plutonium isotopes), coupled with hydrological and bathymetric data, lead to a precise dating of the sediment cores collected at the two sites. (137)Cs signals originating from global fallout (early 1960s) and from the Chernobyl accident (1986) are identified, but at different levels due to the incomplete nature or variable continuity of the records. Anomalous (238)Pu concentrations found at both sites (1-2 Bq kg(-1)) are attributed to unknown industrial releases originating from upstream. Interpolating (137)Cs sediment activities under the assumption of a constant sediment rate, those releases were dated back to 1975 ± 1, thus providing a local but reliable time-marker. Age models have highlighted a very contrasting sediment filling dynamics in these two sites. This study presents the first sediment record of alpha- and gamma-emitting artificial radionuclides obtained at the outlet of the huge catchment area of the River Seine, over a period covering the last 50 years.

Impact of copper on the abundance and diversity of sulfate-reducing prokaryotes in two chilean marine sediments.

We studied the abundance and diversity of the sulfate-reducing prokaryotes (SRPs) in two 30-cm marine chilean sediment cores, one with a long-term exposure to copper-mining residues, the other being a non-exposed reference sediment. The abundance of SRPs was quantified by qPCR of the dissimilatory sulfite reductase gene ß-subunit (dsrB) and showed that SRPs are sensitive to high copper concentrations, as the mean number of SRPs all along the contaminated sediment was two orders of magnitude lower than in the reference sediment. SRP diversity was analyzed by using the dsrB-sequences-based PCR-DGGE method and constructing gene libraries for dsrB-sequences. Surprisingly, the diversity was comparable in both sediments, with dsrB sequences belonging to Desulfobacteraceae, Syntrophobacteraceae, and Desulfobulbaceae, SRP families previously described in marine sediments, and to a deep branching dsrAB lineage. The hypothesis of the presence of horizontal transfer of copper resistance genes in the microbial population of the polluted sediment is discussed.