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Several novel phosphoramidites have been prepared by reaction of the primary amines para-vinylaniline, ortho-anisidine, 2-methoxyphenyl(4-vinylbenzyl)amine, 8-aminoquinoline and 3-vinyl-8-aminoquinoline with (S)-1,1′-bi-2-naphthylchlorophosphite, in the presence of base. Rhodium(I) complexes of these phosphoramidites catalyse the asymmetric hydrogenation of dimethylitaconate and dehydroamino acids and esters giving ee values up to 95%. Soluble non-cross linked polymers of the para-vinylaniline and 3-vinyl-8-aminoquinoline-based phosphoramidites have been prepared by free radical co-polymerisation with styrene in the presence of AIBN as initiator. The corresponding [Rh(COD)]+ complexes serve as recyclable catalysts for the asymmetric hydrogenation dimethylitaconate and dehydroamino acids and esters to give ee values up to 80%. [Copyright &y& Elsevier]

Abstract: Two S-[18F]fluoroalkylated diarylguanidines were synthesized and evaluated in vitro as potential tracers for imaging of N-methyl-d-aspartate receptors (NMDARs) with positron emission tomography (PET). [18F]1 and [18F]10 were synthesized by [18F]fluoroethylation and [18F]fluoromethylation of the thiol precursor 6, respectively. [18F]1 is a promising candidate NMDAR PET tracer, with low nanomolar affinity for the NMDA PCP-site, high selectivity and moderate lipophilicity. [Copyright &y& Elsevier]

The classification of prostate cancer (PCa) lesions using Prostate Imaging Reporting and Data System (PI-RADS) suffers from poor inter-reader agreement. This study compared quantitative parameters or radiomic features from multiparametric magnetic resonance imaging (mpMRI) or positron emission tomography (PET), as inputs into machine learning (ML) to predict the Gleason scores (GS) of detected lesions for improved PCa lesion classification. 20 biopsy-confirmed PCa subjects underwent imaging before radical prostatectomy. A pathologist assigned GS from tumour tissue. Two radiologists and one nuclear medicine physician delineated the lesions on the mpMR and PET images, yielding 45 lesion inputs. Seven quantitative parameters were extracted from the lesions, namely T2-weighted (T2w) image intensity, apparent diffusion coefficient (ADC), transfer constant (KTRANS), efflux rate constant (K ep), and extracellular volume ratio (V e) from mpMR images, and SUV mean and SUV max from PET images. Eight radiomic features were selected out of 109 radiomic features from T2w, ADC and PET images. Quantitative parameters or radiomic features, with risk factors of age, prostate-specific antigen (PSA), PSA density and volume, of 45 different lesion inputs were input in different combinations into four ML models - Decision Tree (DT), Support Vector Machine (SVM), k-Nearest-Neighbour (kNN), Ensembles model (EM). SUV max yielded the highest accuracy in discriminating detected lesions. Among the 4 ML models, kNN yielded the highest accuracies of 0.929 using either quantitative parameters or radiomic features with risk factors as input. ML models' performance is dependent on the input combinations and risk factors further improve ML classification accuracy. [Display omitted] • Among 7 quantitative parameters, SUV max correlated best with Gleason score (GS). • Machine learning yielded higher accuracies than using cut-points of parameters. • Quantitative parameters (QP) and radiomic features (RF) as inputs for GS prediction. • K-Nearest Neighbour yielded highest accuracy of 0.929 with QP and RF. • Combinations of parameters, risk factors and models affect classification accuracy. [ABSTRACT FROM AUTHOR]

Abstract: An intravascular MRI contrast agent Gd(DO3A-Lys), Gadolinium(III) (2,2′,2″-(10-(3-(5-benzamido-6-methoxy-6-oxohexylamino)-3-oxopropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate), has been studied for tumor angiography based on its high relaxivity and long blood half-life. The preparation procedures of the contrast agent have been modified in order to achieve higher yield and improve the synthetic reproducibility. High relaxivity of Gd(DO3A-Lys) has been confirmed by measurements at 3 T, 7 T and 9.4 T magnetic fields. The relaxivity-dependent albumin binding study indicated that Gd(DO3A-Lys) partially bound to albumin protein. In vitro cell viability in HK2 cell indicated low cytotoxicity of Gd(DO3A-Lys) up to 1.2 mm [Gd] concentration. In vivo toxicity studies demonstrated no toxicity of Gd(DO3A-Lys) on kidney tissues up to 0.2 mm [Gd]. While the toxicity on liver tissue was not observed at low dosage (1.0 mm [Gd]), Gd(DO3A-Lys) cause certain damage on hepatic tissue at high dosage (2.0 mm [Gd]). The DO3A-Lys has been labeled with 68Ga radioisotope for biodistribution studies. 68Ga(DO3A-Lys) has high uptake in both HT1080 and U87MG xenograft tumors, and has high accumulation in blood. Contrast-enhanced MR angiography (CE-MRA) in mice bearing U87MG xenograft tumor demonstrated that Gd(DO3A-Lys) could enhance vascular microenvironment around the tumor, and displays promising characteristics of an MRI contrast agent for tumor angiography. [Copyright &y& Elsevier]

Abstract: A series of novel TSPO ligands based on the tetracyclic class of translocator protein (TSPO) ligands first described by Okubo et al. was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands. [Copyright &y& Elsevier]

Abstract: We report here a radiosynthesis for the D2/3 agonist (+)-4-([3-11C]propyl)-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol (3-[11C]-(+)-PHNO) labelled at the terminal carbon of the N-propyl chain. The protocol is based on 11C-methylation of an N-acetyl precursor. This initial step is followed by a reduction with LiAlH4 to give ([3-11C]-(+)-PHNO). We first applied the method for the synthesis of a model compound, N-3-([11C]propyl)-1,2,3,4-tetrahydroisoquinoline, which we obtained in 77–97% analytical radiochemical yield (n=6) in 20min. Similarly, we prepared ([3-11C]-(+)-PHNO) in 55–60% analytical radiochemical yield (n=5) using a one-pot procedure. We have also been able to implement the complete process on a semi-automated module. This platform delivered purified and formulated [3-11C]PHNO with an average radiochemical yield of 9% (n=13, range 2–30%, non-decay corrected), a radiochemical purity >95%, and a specific radioactivity of 26.8–81.1GBq/μmol in a total time of 63–65min. [Copyright &y& Elsevier]

Abstract: A series of organic cations, such as triphenylphosphonium (TPP), 2-(diphenylphosphoryl)-ethyldiphenylphosphonium (TPEP), represent molecular probes for imaging tumors. These organic cations have been labeled with 64Cu radioisotope for imaging tumors by positron emission tomograghy (PET). Among these organic cation ligands, TPEP was selected for extensive evaluation using magnetic resonance imaging (MRI) based on its higher tumor uptake and better Tumor/Background (T/B) ratios. This report presents the development of a new Gd(III) chelate [Gd(DO3A-xy-TPEP)]+ as a cationic MRI contrast agent. The contrast agent was synthesized and characterized in vitro and in vivo. In vitro cell viability showed low cytotoxicity at low [Gd] concentrations. Cell uptake experiment shows that the [Gd(DO3A-xy-TPEP)]+ has high affinity for tumor cells. The in vitro T 1 relaxivity measured at 9.4 T is about 50% higher than those of contrast agents in clinical use: Gd-DTPA (Magnevist) and Gd-DOTA (Dotarem). In vivo imaging studies in tumor-bearing mice at 7.0 T demonstrated significant signal enhancement at the site of the tumors. [Gd(DO3A-xy-TPEP)]+ is a promising tumor-targeting MRI contrast agent for diagnostic imaging. [Copyright &y& Elsevier]

Abstract: A novel class of alkyne linked [Tyr3]octreotate analogues have been labelled by a copper catalysed azide-alkyne cycloaddition reaction (CuAAC) to form a 1,4-substituted triazole using the reagent [18F]2-fluoroethyl azide. An unexpected variability in reactivity during the CuAAC reaction was observed for each alkyne analogue which has been investigated. Two lead alkyne linked [Tyr3]octreotate analogues, G-TOCA (3a) and βAG-TOCA (5a) have been identified to be highly reactive in the click reaction showing complete conversion to the [18F]2-fluoroethyl triazole linked [Tyr3]octreotate analogues FET-G-TOCA (3b) and FET-βAG-TOCA (5b) under mild conditions and with short synthesis times (5min at 20°C). As well as ease of synthesis, in vitro binding to the pancreatic tumour AR42J cells showed that both FET-G-TOCA and FET-βAG-TOCA have high affinity for the somatostatin receptor with IC50 of 4.0±1.4, and 1.6±0.2nM, respectively. [Copyright &y& Elsevier]

Abstract: Introduction: Choline radiotracers are widely used for clinical PET diagnosis in oncology. [11C]Choline finds particular utility in the imaging of brain and prostate tumor metabolic status, where 2-[18F]fluoro-2-deoxy-d-glucose (‘FDG’) shows high background uptake. More recently we have extended the clinical utility of [11C]choline to breast cancer where radiotracer uptake correlates with tumor aggressiveness (grade). In the present study, a new choline analog, [18F]fluoro-[1,2-2H4]choline, was synthesized and evaluated as a potential PET imaging probe. Methods: [18F]Fluorocholine, [18F]fluoro-[1-2H2]choline and [18F]fluoro-[1,2-2H4]choline were synthesized by alkylation of the relevant precursor with [18F]fluorobromomethane or [18F]fluoromethyl tosylate. Radiosynthesis of [18F]fluoromethyl tosylate required extensive modification of the existing method. [18F]Fluorocholine and [18F]fluoro-[1,2-2H4]choline were then subjected to in vitro oxidative stability analysis in a chemical oxidation model using potassium permanganate and an enzymatic model using choline oxidase. The two radiotracers, together with the corresponding di-deuterated compound, [18F]fluoro-[1-2H2]choline, were then evaluated in vivo in a time-course biodistribution study in HCT-116 tumor-bearing mice. Results: Alkylation with [18F]fluoromethyl tosylate proved to be the most reliable radiosynthetic route. Stability models indicate that [18F]fluoro-[1,2-2H4]choline possesses increased chemical and enzymatic (choline oxidase) oxidative stability relative to [18F]fluorocholine. The distribution of the three radiotracers, [18F]fluorocholine, [18F]fluoro-[1-2H2]choline and [18F]fluoro-[1,2-2H4]choline, showed a similar uptake profile in most organs. Crucially, tumor uptake of [18F]fluoro-[1,2-2H4]choline was significantly increased at late time points compared to [18F]fluorocholine and [18F]fluoro-[1-2H2]choline. Conclusions: Stability analysis and biodistribution suggest that [18F]fluoro-[1,2-2H4]choline warrants further in vivo investigation as a PET probe of choline metabolism. [Copyright &y& Elsevier]

The compound [Rh(COE)2(acac)] (1) is a catalyst precursor in its own right, and a starting material for the preparation of other catalyst precursors for use in a variety of reactions such as hydroboration, diboration and the addition of arylboronic acids to aldehydes. Although a preparation using Tl(acac) and [Rh(COE)2(μ-Cl)]2 is in the literature, it would appear that it is not widely known and we have received several requests for our synthetic protocol for 1, which does not use any thallium salts. We present herein a synthesis of 1 from [Rh(COE)2(μ-Cl)]2 and Na(acac), along with its full spectroscopic and structural characterisation. The single crystal X-ray structure of 1 indicates approximate square-planar geometry at Rh, with the two olefinic C&z.dbnd6;C bonds lying perpendicular to the square plane. [Copyright &y& Elsevier]