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Comprehensive Summary: Compared to well‐established 1,5‐HAT of N‐centered radicals, the synthetic applications of 1,2‐HAT process were scarce due to the high barrier and constrained three‐membered transition state. Here, we have developed a novel C(sp3)‐H gem‐difluoroallylation via a base assisted formal 1,2‐HAT of amidyl radicals with the reductive quenching cycle of photocatalyst. This transformation enables the efficient formation of α‐aminoalkyl radicals via 1,2‐HAT and showcases good functional group tolerance. Our preliminary mechanistic experiments, along with Density Functional Theory (DFT) calculations demonstrate the feasibility of 1,2‐HAT of amidyl radicals, especially when assisted by a base. Furthermore, our method also succeeds in the Giese addition of electron‐deficient alkenes as well as styrene. [ABSTRACT FROM AUTHOR]

Herein we report the automation and scale-up of a photofluorination process key to the production of branched-chain aliphatic radiotracers such as (S)-5-[18F]fluorohomoleucine ((S)-5-[18F]]FHL). (S)-5-[18F]FHL is a leucine analogue that is primarily taken up by the L-type amino acid transporter (LAT or System L). LAT1 expression levels correlate closely with tumor proliferation, angiogenesis, and treatment outcomes, making it an attractive target for molecular imaging of cancer. We have previously synthesized (S)-5-[18F]FHL and tested this tracer in mice bearing PC3 (prostate) or U87 (glioma) xenografts in order to establish its feasibility for detecting and monitoring treatment for a broad range of cancers. In this study, the radiosynthesis of 5-[18F]FHL is demonstrated on an automated DT-PhotoFluor module with a radiochemical yield of 20.1 ± 4.8% (n = 3), radiochemical purity of 94.5 ± 4.9% (n = 3), and a synthesis time of ~ 75 min. The reported DT-PhotoFluor module will allow for higher molar activity, better reproducibility, and reduced radiation exposure for upcoming first-in-human studies. [ABSTRACT FROM AUTHOR]

Due to their high lipophilicity and strong electron‐withdrawing property, more and more attention has been paid to introducing trifluoromethylseleno and fluoroalkylseleno moieties into organic molecules. In this short review, we categorize the synthesis of compounds that combine selenium and fluorinated moieties into two main types: trifluoromethylselenolation (CF3Se) and fluoroalkylselenolation (RfSe, except CF3Se). This review aims to provide a summary of the recent advances in direct C−H trifluoromethylselenolation and fluoroalkylselenolation from the synthesis of trifluoromethylselenolation and fluoroalkylselenolation reagents to their application. Based on the method of how the RfSe group was introduced, the main content is divided into three parts: transition‐metal‐free reactions, transition‐metal‐mediated/catalyzed reactions and photo‐catalyzed reactions. The general substrate scope, mechanism and limitations would also be discussed so that we hope the review will serve as an inspiration for further research in this appealing research field. [ABSTRACT FROM AUTHOR]

Herein, the tandem synthesis of various CF3Se‐containing heterocyclic compounds has been developed, using Tf2O as the catalyst and trifluoromethyl selenoxides as the electrophilic trifluoromethylselenolation reagents. This process is characterized by its mild conditions, ease of operation, and good functional group compatibility. A variety of alkynes could be transferred into CF3Se‐containing indoles, benzofurans, benzothiophenes, isoquinolines and chromenes in good yields. A key step involving the formation of the electrophilic CF3Se species was proposed. [ABSTRACT FROM AUTHOR]

Terbium radioisotopes (149Tb, 152Tb, 155Tb, 161Tb) offer a unique class of radionuclides which encompass all four medicinally relevant nuclear decay modalities (α, β+, γ, β−/e−), and show high potential for the development of element-matched theranostic radiopharmaceuticals. The goal of this study was to design, synthesise, and evaluate the suitability of crown-TATE as a new peptide-conjugate for radiolabelling of [155Tb]Tb3+ and [161Tb]Tb3+, and to assess the imaging and pharmacokinetic properties of each radiotracer in tumour-bearing mice. [155Tb]Tb-crown-TATE and [161Tb]Tb-crown-TATE were prepared efficiently under mild conditions, and exhibited excellent stability in human serum (>99.5% RCP over 7 days). Longitudinal SPECT/CT images were acquired for 155Tb- and 161Tb- labelled crown-TATE in male NRG mice bearing AR42J tumours. The radiotracers, [155Tb]Tb-crown-TATE and [161Tb]Tb-crown-TATE, showed high tumour targeting (32.6 and 30.0 %ID/g, respectively) and minimal retention in non-target organs at 2.5 h post-administration. Biodistribution studies confirmed the SPECT/CT results, showing high tumour uptake (38.7 ± 8.0 %ID/g and 38.5 ± 3.5 %ID/g, respectively) and favourable tumour-to-background ratios. Blocking studies further confirmed SSTR2-specific tumour accumulation. Overall, these findings suggest that crown-TATE has great potential for element-matched molecular imaging and radionuclide therapy using 155Tb and 161Tb. [ABSTRACT FROM AUTHOR]

Here we report that the selective trifluoromethylthiolation of unactivated C(sp3)−H bonds is enabled by photoexcited diaryl ketones. This method for C−H trifluoromethylthiolation features mild conditions and inexpensive organic photocatalysts and relies on 370 nm LED lights. The functional group tolerance is broad and the excellent regioselectivity for branched aliphatic positions enables trifluoromethylthiolation of a variety of substrates, including amino acid and natural product derivatives, demonstrating its potential synthetic application. [ABSTRACT FROM AUTHOR]

Targeted alpha‐therapy (TAT) has great potential for treating a broad range of late‐stage cancers by delivering a focused and lethal radiation dose to tumors. Actinium‐225 (225Ac) is an emerging alpha emitter suitable for TAT; however, the availability of chelators for Ac remains limited to a small number of examples (DOTA and macropa). Herein, we report a new Ac macrocyclic chelator named 'crown', which binds quantitatively and rapidly (<10 min) to Ac at ambient temperature. We synthesized 225Ac‐crown‐αMSH, a peptide targeting the melanocortin 1 receptor (MC1R), specifically expressed in primary and metastatic melanoma. Biodistribution of 225Ac‐crown‐αMSH showed favorable tumor‐to‐background ratios at 2 h post injection in a preclinical model. In addition, we demonstrated dramatically different biodistrubution patterns of 225Ac‐crown‐αMSH when subjected to different latency times before injection. A combined quality control methodology involving HPLC, gamma spectroscopy and radioTLC is recommended. [ABSTRACT FROM AUTHOR]

Peptides are often ideal ligands for diagnostic molecular imaging due to their ease of synthesis and tuneable targeting properties. However, labelling unmodified peptides with 18F for positron emission tomography (PET) imaging presents a number of challenges. Here we show the combination of photoactivated sodium decatungstate and [18F]‐N‐fluorobenzenesulfonimide effects site‐selective 18F‐fluorination at the branched position in leucine residues in unprotected and unaltered peptides. This streamlined process provides a means to directly convert native peptides into PET imaging agents under mild aqueous conditions, enabling rapid discovery and development of peptide‐based molecular imaging tools. [ABSTRACT FROM AUTHOR]