Development of PDT/PET theranostics: synthesis and biological evaluation of an ¹⁸F-radiolabeled water soluble porphyrin

Synthesis of the first water-soluble porphyrin radiolabeled with fluorine-18 is described: a new molecular theranostic agent which integrates the therapeutic selectivity of photodynamic therapy (PDT) with the imaging efficacy of positron emission tomography (PET). Generation of the theranostic was carried out through the conjugation of a cationic water-soluble porphyrin bearing an azide functionality to a fluorine-18 radiolabeled prosthetic bearing an alkyne functionality through click conjugation, with excellent yields obtained in both cold and hot synthesis. Biological evaluation of the synthesized structures shows the first example of an 18 F-radiolabeled porphyrin retaining photocytotoxicity following radiolabeling and demonstrable conjugate uptake and potential application as a radiotracer in vivo. The promising results gained from biological evaluation demonstrate the potential of this structure as a clinically relevant theranostic agent, offering exciting possibilities for the simultaneous imaging and photodynamic treatment of tumors

Fluvial organic carbon flux from an eroding peatland catchment, southern Pennines, UK

This study investigates for the first time the relative importance of dissolved organic carbon (DOC) and particulate organic carbon (POC) in the fluvial carbon flux from an actively eroding peatland catchment in the southern Pennines, UK. Event scale variability in DOC and POC was examined and the annual flux of fluvial organic carbon was estimated for the catchment. At the event scale, both DOC and POC were found to increase with discharge, with event based POC export accounting for 95% of flux in only 8% of the time. On an annual cycle, exports of 35.14 t organic carbon (OC) are estimated from the catchment, which represents an areal value of 92.47 g C m<sup>−2</sup> a<sup>−1</sup>. POC was the most significant form of organic carbon export, accounting for 80% of the estimated flux. This suggests that more research is required on both the fate of POC and the rates of POC export in eroding peatland catchments

Spatial variability of nitrate concentration in lakes in Snowdonia, North Wales, UK

International audienceAt a regional scale, high nitrate (NO3?) concentrations in upland surface waters generally occur in tandem with high nitrogen (N) deposition levels. However, significant differences in the patterns of surface water NO3? concentration have been observed within areas of similar N deposition yet relatively few studies have been undertaken which examine within-region variation of NO3? concentrations. A study of 76 lakes in Snowdonia, north Wales, an area of high deposition and sensitive catchments, was undertaken to assess variation in surface water NO3? concentration across a 20 x 20 km grid square and to identify catchments vulnerable to NO3? leaching. Nitrate concentrations vary considerably, particularly during winter when values range from 0.7 to 70 ?eq l-1. Although retention by vegetation and soil microbes in summer reduces the amount of NO3? reaching the lakes, 37 % of sites are characterised by NO3? concentrations greater then 4 ?eq l-1. The elevated concentrations occurring in summer suggests that N breakthrough has occurred. By examining the ratio of NO3? to total strong acid anions, it is shown that NO3? contributes significantly to freshwater acidity, particularly during the winter. Redundancy analysis shows that NO3? leaching is greatest, both in winter and summer, in catchments with high proportions of bare rock where soil and vegetation cover is limited. Nitrogen cycling in these catchments, generally at higher altitudes, may no longer be governed by seasonal biological controls. They are likely to be saturated with respect to nitrogen (i.e. incapable of further N retention) as a result of the elevated deposition levels in the area. The contribution of NO3? to acidity is also greatest at these sites. In winter, significant positive relationships are also evident between NO3? concentration and soil pH and coniferous woodland. The study demonstrates the importance of catchment factors in modifying the relationship between N deposition and N leaching in upland catchments

Fluvial organic carbon flux from an eroding peatland catchment, southern Pennines, UK

International audienceThis study investigates for the first time the relative importance of dissolved organic carbon (DOC) and particulate organic carbon (POC) in the fluvial carbon flux from an actively eroding peatland catchment in the southern Pennines, UK. Event scale variability in DOC and POC was examined and the annual flux of fluvial organic carbon was estimated for the catchment. At the event scale, both DOC and POC were found to increase with discharge, with event based POC export accounting for 95% of flux in only 8% of the time. On an annual cycle, 40.8 t organic carbon (OC) is exported from the catchment, which represents an areal value of 107 gC m?2 a?1. POC was the most significant form of organic carbon export, accounting for ~82% of the estimated flux. This suggests that more research is required on both the fate of POC and the rates of POC export in eroding peatland catchments

Interrelationships between depressive symptoms and positive and negative symptoms of recent onset schizophrenia spectrum disorders:A network analytical approach

Objective: There is a need to better understand the interrelationships between positive and negative symptoms of recent-onset schizophrenia spectrum disorders (SSD) and co-occurring depressive symptoms. Aims were to determine: (1) whether depressive symptoms are best conceptualised as distinct from, or intrinsic to, positive and negative symptoms; and (2) bridging symptoms. Methods: Network analysis was applied to data from 198 individuals with depressive and psychotic symptoms in SSD from the Psychosis Recent Onset GRoningen Survey (PROGR-S). Measures were: Montgomery-Asberg Depression Rating Scale and Positive and Negative Syndrome Scale. Results: Positive symptoms were just as likely to be associated with depressive and negative symptoms, and had more strong associations with depressive than negative symptoms. Negative symptoms were more likely to be associated with depressive than positive symptoms, and had more strong associations with depressive than positive symptoms. Suspiciousness and stereotyped thinking bridged between positive and depressive symptoms, and apparent sadness and lassitude between negative and depressive symptoms. Conclusions: Depressive symptoms might be best conceptualised as intrinsic to positive and negative symptoms pertaining to deficits in motivation and interest in the psychotic phase of SSD. Treatments targeting bridges between depressive and positive symptoms, and depressive and such negative symptoms, might prevent or improve co-occurring depressive symptoms, or vice-versa, in the psychotic phase of SSD

A practical guide to automating fluorine-18 PET radiochemistry using commercially available cassette-based platforms

The automation of positron emission tomography (PET) radiochemistry using cassette-based automated radiosynthesis platforms is an essential component of clinical translation for the vast majority of 18F-based radiopharmaceuticals. The technology is widely adopted by good manufacturing practice (GMP) compliant radiopharmaceutical production facilities and research institutions developing novel tracers for clinical studies. Despite automation being fundamental to clinical translation, educational resources which introduce this branch of radiochemistry to the uninitiated are limited. Publications featuring automation assume previous experience of using these platforms and therefore, the detail they provide may not be sufficient for a novice user. In this Tutorial Account, we aim to bridge this knowledge gap and provide a resource for efficient automation for radiochemists across all levels of experience

A New Architecture for DNA‐Templated Synthesis in Which Abasic Sites Protect Reactants from Degradation

The synthesis of artificial sequence‐defined polymers that match and extend the functionality of proteins is an important goal in materials science. One way of achieving this is to program a sequence of chemical reactions between precursor building blocks by means of attached oligonucleotide adapters. However, hydrolysis of the reactive building blocks has so far limited the length and yield of product that can be obtained using DNA‐templated reactions. Here, we report an architecture for DNA‐templated synthesis in which reactants are tethered at internal abasic sites on opposite strands of a DNA duplex. We show that an abasic site within a DNA duplex can protect a nearby thioester from degradation, significantly increasing the yield of a DNA‐templated reaction. This protective effect has the potential to overcome the challenges associated with programmable, sequence‐controlled synthesis of long non‐natural polymers by extending the lifetime of the reactive building blocks

A New Architecture for DNA‐Templated Synthesis in Which Abasic Sites Protect Reactants from Degradation

The synthesis of artificial sequence‐defined polymers that match and extend the functionality of proteins is an important goal in materials science. One way of achieving this is to program a sequence of chemical reactions between precursor building blocks by means of attached oligonucleotide adapters. However, hydrolysis of the reactive building blocks has so far limited the length and yield of product that can be obtained using DNA‐templated reactions. Here, we report an architecture for DNA‐templated synthesis in which reactants are tethered at internal abasic sites on opposite strands of a DNA duplex. We show that an abasic site within a DNA duplex can protect a nearby thioester from degradation, significantly increasing the yield of a DNA‐templated reaction. This protective effect has the potential to overcome the challenges associated with programmable, sequence‐controlled synthesis of long non‐natural polymers by extending the lifetime of the reactive building blocks

A new architecture for DNA-templated synthesis in which abasic sites protect reactants from degradation

The synthesis of artificial sequence-defined polymers that match and extend the functionality of proteins is an important goal in materials science. One way of achieving this is to program a sequence of chemical reactions between precursor building blocks by means of attached oligonucleotide adapters. However, hydrolysis of the reactive building blocks has so far limited the length and yield of product that can be obtained using DNA-templated reactions. Here, we report an architecture for DNA-templated synthesis in which reactants are tethered at internal abasic sites on opposite strands of a DNA duplex. We show that an abasic site within a DNA duplex can protect a nearby thioester from degradation, significantly increasing the yield of a DNA-templated reaction. This protective effect has the potential to overcome the challenges associated with programmable sequence-controlled synthesis of long non-natural polymers by extending the lifetime of the reactive building blocks