Cyclotron-Based Production of Cu for Radionuclide Theranostics via the Zn(p,α)Cu Reaction.

Theranostic matched pairs of radionuclides have aroused interest during the last couple of years, and in that sense, copper is one element that has a lot to offer, and although Cu and Cu are slowly being established as diagnostic radionuclides for PET, the availability of the therapeutic counterpart Cu plays a key role for further radiopharmaceutical development in the future. Until now, the Cu shortage has not been solved; however, different production routes are being explored. This project aims at the production of no-carrier-added Cu with high radionuclidic purity with a medical 30MeV compact cyclotron via the Zn(p,α)Cu reaction.

Synthesis of [F]FMISO, a hypoxia-specific imaging probe for PET, an overview from a radiochemist's perspective.

Background: [F]fluoromisonidazole ([F]FMISO, 1H-1-(3-[F]fluoro-2-hydroxypropyl)-2-nitroimidazole) is a commonly used radiotracer for imaging hypoxic conditions in cells. Since hypoxia is prevalent in solid tumors, [F]FMISO is in clinical application for decades to explore oxygen demand in cancer cells and the resulting impact on radiotherapy and chemotherapy.

Results: Since the introduction of [F]FMISO as positron emission tomography imaging agent in 1986, a variety of radiosynthesis procedures for the production of this hypoxia tracer has been developed.

Exploring Nitric Oxide (NO)-Releasing Celecoxib Derivatives as Modulators of Radioresponse in Pheochromocytoma Cells.

COX-2 can be considered as a clinically relevant molecular target for adjuvant, in particular radiosensitizing treatments. In this regard, using selective COX-2 inhibitors, e.g.

Stroke Angel: Effect of Telemedical Prenotification on In-Hospital Delays and Systemic Thrombolysis in Acute Stroke Patients.

Introduction: Door-to-CT scan time (DCT) and door-to-needle time (DNT) are important process measures in acute ischemic stroke (AIS) patients undergoing intravenous thrombolysis (IVT). We examined the impact of a telemedical prenotification by emergency medical service (EMS) (called the "Stroke Angel" program) on DCT and DNT and IVT rate compared to standard of care.

Patients And Methods: Two prospective observational studies including AIS patients admitted via EMS from 2011 to 2013 (cohort I; n = 496) and from January 1, 2015 to May 31, 2018 (cohort II; n = 349) were conducted.

Synthesis and Cyclooxygenase Inhibition of Sulfonamide-Substituted (Dihydro)Pyrrolo[3,2,1-]indoles and Their Potential Prodrugs.

Non-invasive imaging of cyclooxygenase-2 (COX-2) by radiolabeled ligands is attractive for the diagnosis of cancer, and novel highly affine leads with optimized pharmacokinetic profile are of great interest for future developments. Recent findings have shown that methylsulfonyl-substituted (dihydro)pyrrolo[3,2,1-]indoles represent highly potent and selective COX-2 inhibitors but possess unsuitable pharmacokinetic properties for radiotracer applications. Based on these results, we herein present the development and evaluation of a second series of sulfonamide-substituted (dihydro)pyrrolo[3,2,1-]indoles and their conversion into the respective more hydrophilic -propionamide-substituted analogs.

Nitric Oxide-Releasing Selective Estrogen Receptor Modulators: A Bifunctional Approach to Improve the Therapeutic Index.

When using selective estrogen receptor modulators (SERMs) in cancer therapy, adverse effects such as endothelial dysfunction have to be considered. Estrogens and, consequently, SERMs regulate the synthesis of vasoactive nitric oxide (NO). We hypothesized that a bifunctional approach combining the antagonistic action of SERMs with a targeted NO release could diminish vascular side effects.

Synthesis and preliminary radiopharmacological characterisation of an C-labelled azadipeptide nitrile as potential PET tracer for imaging of cysteine cathepsins.

An O-methyltyrosine-containing azadipeptide nitrile was synthesised and investigated for its inhibitory activity towards cathepsins L, S, K, and B. Labelling with carbon-11 was accomplished by reaction of the corresponding phenolic precursor with [ C]methyl iodide starting from cyclotron-produced [ C]methane. Radiopharmacological evaluation of the resulting radiotracer in a mouse xenograft model derived from a mammary tumour cell line by small animal PET imaging indicates tumour targeting with complex pharmacokinetics.

Fluorine-18 Labeling of S100 Proteins for Small Animal Positron Emission Tomography.

The interaction of S100 proteins (S100s), a multigenic family of Ca-binding and Ca-modulated proteins, with pattern recognition receptors, e.g., Toll-like receptors (TLRs), the receptor for advanced glycation end products (RAGE), or scavenger receptors (SR), is hypothesized to be of high relevance in the pathogenesis of various diseases.

[Acceptance, demand, reasons for consultation and outcome of counseling on epilepsy in Hesse and Lower Franconia].

Background And Aim: The diagnosis of epilepsy is often accompanied by relevant restrictions for patients, which may result in disease-specific daily problems that need targeted and professional counseling. Specialized epilepsy counseling services (ECS) were introduced in some German states since 1996 to provide an additional and independent service for epilepsy-related problems. The objective of this prospective, multicenter cohort study at six ECS was to determine and analyze the acceptance, demand and frequent reasons for consultation in Hesse and Lower Franconia.

Access to F-labelled isoxazoles by ruthenium-promoted 1,3-dipolar cycloaddition of 4-[ F]fluoro-N-hydroxybenzimidoyl chloride with alkynes.

4-[ F]Fluoro-N-hydroxybenzimidoyl chloride ( FBIC), an F-labelled aromatic nitrile oxide, was developed as building block for Ru-promoted 1,3-dipolar cycloaddition with alkynes. FBIC is obtained in a one-pot synthesis in up to 84% radiochemical yield (RCY) starting from [ F]fluoride with 4-[ F]fluorobenzaldehyde ( FBA) and 4-[ F]fluorobenzaldehyde oxime ( FBAO) as intermediates, by reaction of FBAO with N-chlorosuccinimide (NCS). FBIC was found to be a suitable and stable synthon to give access to F-labelled 3,4-diarylsubstituted isoxazoles by [Cp*RuCl(cod)]-catalysed 1,3-dipolar cycloaddition with various alkynes.

Counseling and social work for people with epilepsy in Germany: A cross-sectional multicenter study on demand, frequent content, patient satisfaction, and burden-of-disease.

Background: The diagnosis of epilepsy is accompanied by relevant personal, interpersonal, and professional restrictions for patients and their caregivers. Specialized epilepsy counseling services (ECS) have been introduced to inform, advise, and support patients with disease-related problems.

Aim And Scope: The objective of this cross-sectional, multicenter study was to determine the demand, typical content, and outcomes of ECS in children, adolescents, and adults in two adjacent German regions of Hessen and Lower Franconia.

Correction: Novel valdecoxib derivatives by ruthenium(ii)-promoted 1,3-dipolar cycloaddition of nitrile oxides with alkynes - synthesis and COX-2 inhibition activity.

[This corrects the article DOI: 10.1039/C7MD00575J.].

Novel valdecoxib derivatives by ruthenium(ii)-promoted 1,3-dipolar cycloaddition of nitrile oxides with alkynes - synthesis and COX-2 inhibition activity.

Novel valdecoxib-based cyclooxygenase-2 inhibitors were synthesized in one step 1,3-dipolar cycloaddition of nitrile oxides with a series of eleven aryl alkynes, six of them described for the first time. Application of Ru(ii)-catalysis leads preferably to the formation of the 3,4-diaryl-substituted isoxazoles, while under thermal heating with base the 3,5-diaryl substitution pattern is favoured. The new the 3,4-diaryl-substituted isoxazoles possessing a small substituent (H and Me) displayed high COX-2 inhibition affinity (IC = 0.

Evaluation of Fluorine-18-Labeled α1(I)-N-Telopeptide Analogs as Substrate-Based Radiotracers for PET Imaging of Melanoma-Associated Lysyl Oxidase.

Accumulating evidence suggests an unequivocal role of lysyl oxidases as key players of tumor progression and metastasis, which renders this enzyme family highly attractive for targeted non-invasive functional imaging of tumors. Considering their function in matrix remodeling, malignant melanoma appears as particularly interesting neoplasia in this respect. For the development of radiotracers that enable PET imaging of the melanoma-associated lysyl oxidase activity, substrates derived from the type I collagen α1 N-telopeptide were labeled with fluorine-18 using -succinimidyl 4-[F]fluorobenzoate ([F]SFB) as prosthetic reagent.

Bridging from Brain to Tumor Imaging: (S)-(-)- and (R)-(+)-[F]Fluspidine for Investigation of Sigma-1 Receptors in Tumor-Bearing Mice.

Sigma-1 receptors (Sig1R) are highly expressed in various human cancer cells and hence imaging of this target with positron emission tomography (PET) can contribute to a better understanding of tumor pathophysiology and support the development of antineoplastic drugs. Two Sig1R-specific radiolabeled enantiomers ()-(-)- and ()-(+)-[F]fluspidine were investigated in several tumor cell lines including melanoma, squamous cell/epidermoid carcinoma, prostate carcinoma, and glioblastoma. Dynamic PET scans were performed in mice to investigate the suitability of both radiotracers for tumor imaging.

Microstructural white matter changes and their relation to neuropsychological deficits in patients with juvenile myoclonic epilepsy.

Objective: Juvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy syndrome. Neuropsychological, electrophysiological, and neuroimaging studies have led to the hypothesis that JME is related to dysfunction of frontal brain regions and mainly frontal thalamocortical networks.

Methods: We investigated possible microstructural white matter abnormalities of 20 patients with JME as compared with 20 healthy control subjects using diffusion tensor imaging (DTI).

Technetium-99m based small molecule radiopharmaceuticals and radiotracers targeting inflammation and infection.

In nuclear medicine, the detection of inflamed and infected lesions is of growing interest. Extensive efforts have been made to develop radiopharmaceuticals specific for inflammation or for discriminating sterile inflammation from infection. Tc is the worldwide most widely used radioisotope for SPECT imaging.

"Hydrous F-fluoroethylation" - Leaving off the azeotropic drying.

The study describes the development of a simple and effective method for F-fluoroethylation -omitting the azeotropic drying step- by elution of a [F]fluoride loaded QMA column with a KCO/K/acetonitrile solution containing 2-3% (v/v) water directly to the 1,2-ethylene glycol-bis-tosylate precursor. In acetonitrile containing 2-3% (v/v) water the labeling agent 2-[F]fluoroethyl tosylate ([F]FETs) was formed in 76-96% non-isolated radiochemical yield. The method was exemplified on the F-fluoroethylation of three COX-2 inhibitors with different core structures.

Development of Fluorinated Non-Peptidic Ghrelin Receptor Ligands for Potential Use in Molecular Imaging.

The ghrelin receptor (GhrR) is a widely investigated target in several diseases. However, the current knowledge of its role and distribution in the brain is limited. Recently, the small and non-peptidic compound ()-6-(4-bromo-2-fluorophenoxy)-3-((1-isopropylpiperidin-3-yl)methyl)-2-methylpyrido[3,2-d]pyrimidin-4(3)-one (()-) has been described as a GhrR ligand with high binding affinity.

Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy-A Hypothesis-Driven Review.

Radiation therapy (RT) evolved to be a primary treatment modality for cancer patients. Unfortunately, the cure or relief of symptoms is still accompanied by radiation-induced side effects with severe acute and late pathophysiological consequences. Inhibitors of cyclooxygenase-2 (COX-2) are potentially useful in this regard because radioprotection of normal tissue and/or radiosensitizing effects on tumor tissue have been described for several compounds of this structurally diverse class.

(18)F-Labeled 1,4-Dioxa-8-azaspiro[4.5]decane Derivative: Synthesis and Biological Evaluation of a σ1 Receptor Radioligand with Low Lipophilicity as Potent Tumor Imaging Agent.

We report the syntheses and evaluation of series of novel piperidine compounds with low lipophilicity as σ1 receptor ligands. 8-(4-(2-Fluoroethoxy)benzyl)-1,4-dioxa-8-azaspiro[4.5]decane (5a) possessed high affinity (K(i) = 5.

Novel (pyrazolyl)benzenesulfonamides with a nitric oxide-releasing moiety as selective cyclooxygenase-2 inhibitors.

Inhibition of cyclooxygenase-2 (COX-2) is a promising anti-inflammatory therapeutic strategy, but long-term medication with COX-2-inhibitors (coxibs) may be associated with adverse cardiovascular effects. Functionalization of existing lead structures with nitric oxide (NO)-releasing moieties is an auspicious approach to minimize these effects. In this regard, an organic nitrate (-O-NO2) substituent was introduced at a (pyrazolyl)benzenesulfonamide lead structure.

Diaryl-Substituted (Dihydro)pyrrolo[3,2,1-hi]indoles, a Class of Potent COX-2 Inhibitors with Tricyclic Core Structure.

A new compound class of diaryl-substituted heterocycles with tricyclic dihydropyrrolo[3,2,1-hi]indole and pyrrolo[3,2,1-hi]indole core structures has been designed and was synthesized by a modular sequence of Friedel-Crafts acylation, amide formation, and McMurry cyclization. This synthesis route represents a novel and versatile access toward dihydropyrrolo[3,2,1-hi]indoles and is characterized by good chemical yields and high modularity. From a set of 19 derivatives, 11 candidates were selected for determination of their COX inhibition potency and were found to be selective inhibitors with high affinity to COX-2 (IC50 ranging from 20-2500 nM and negligible inhibition of COX-1).