Exploration of commercial cyclen-based chelators for mercury-197 m/g incorporation into theranostic radiopharmaceuticals.

A comprehensive investigation of the Hg coordination chemistry and Hg radiolabeling capabilities of cyclen-based commercial chelators, namely, DOTA and DOTAM (aka TCMC), along with their bifunctional counterparts, -SCN-Bn-DOTA and -SCN-Bn-TCMC, was conducted to assess the suitability of these frameworks as bifunctional chelators for the Hg theranostic pair. Radiolabeling studies revealed that TCMC and DOTA exhibited low radiochemical yields (0%-6%), even when subjected to harsh conditions (80°C) and high ligand concentrations (10 M). In contrast, -SCN-Bn-TCMC and -SCN-Bn-DOTA demonstrated significantly higher Hg radiochemical yields (100% ± 0.

Evaluation of a novel hexadentate 1,2-hydroxypyridinone-based acyclic chelate, HOPO-O-C4, for Sc/Sc, Ga, and Ti radiopharmaceuticals.

Introduction: Chelators play a crucial role in the development of metal-based radiopharmaceuticals, and with the continued interest in Ga and increasing availability of new radiometals such as Sc/Sc and Ti, there is a growing demand for tailored chelators that can form stable complexes with these metals. This work reports the synthesis and characterization of a hexadentate tris-1,2-hydroxypyridonone chelator HOPO-O-C4 and its in vitro and in vivo evaluation with the above mentioned radiometals.

Methods: To investigate the affinity of HOPO-O-C4, macroscopic studies were performed with Sc, and Ga followed by DFT structural optimization of the Sc, Ga and Ti complexes.

Technetium Nitrido Complexes of Tetradentate Thiosemicarbazones: Kit-Based Radiolabeling, Characterization, and Evaluation.

Bis(thiosemicarbazone) and pyridylhydrazone-thiosemicarbazone chelators have demonstrated utility in nuclear medicine. In particular, the Cu complexes have been extensively developed for hypoxia imaging and molecular imaging of peptide and protein markers of disease. However, the chemistry and application of bis(thiosemicarbazone) and pyridylhydrazone-thiosemicarbazone chelators in combination with Tc, the most widely used radionuclide in nuclear medicine, is underexplored.

Modern Developments in Bifunctional Chelator Design for Gallium Radiopharmaceuticals.

The positron-emitting radionuclide gallium-68 has become increasingly utilised in both preclinical and clinical settings with positron emission tomography (PET). The synthesis of radiochemically pure gallium-68 radiopharmaceuticals relies on careful consideration of the coordination chemistry. The short half-life of 68 min necessitates rapid quantitative radiolabelling (≤10 min).

Hexadentate technetium-99m bis(thiosemicarbazonato) complexes: synthesis, characterisation and biodistribution.

The syntheses of non-oxido/non-nitrido bis(thiosemicarbazonato)technetium(V) complexes featuring a series of alkyl and ether substituents is presented. The bis(thiosemicarbazones) were radiolabelled with technetium-99m using an optimised one-pot synthesis from [Tc][TcO]. Mass spectrometry and computational chemistry data suggested a distorted trigonal prismatic coordination environment for the bis(thiosemicarbazonato)technetium(V) complexes by way of a bis(thiosemicarbazone)technetium(V)-oxido intermediate complex.

Assessment and Mitigation of Cardiovascular Risk for Prostate Cancer Patients: A Review of the Evidence.

Background: Cardiovascular disease (CVD) is a common comorbidity in patients with prostate cancer. In this review, we summarize the published literature on the association of cardiovascular risk with androgen deprivation therapy (ADT) treatment and explore the potential differences between the gonadotropin-releasing hormone (GnRH) agonists and antagonists and the molecular mechanisms that may be involved. We also provide a practical outlook on the identification of underlying CV risk and explore the different stratification tools available.

The Synthesis of a Bis(thiosemicarbazone) Macrocyclic Ligand and the Mn(II), Co(II), Zn(II) and Ga(III) Complexes.

A 1,4,7,10-tetraazacyclododecane (cyclen) variant bearing two thiosemicarbazone pendant groups has been prepared. The ligand forms complexes with Mn, Co and Zn. X-ray crystallography of the Mn, Co and Zn complexes showed that the ligand provides a six-coordinate environment for the metal ions.

An octadentate bis(semicarbazone) macrocycle: a potential chelator for lead and bismuth radiopharmaceuticals.

A variant of 1,4,7,10-tetraazacyclododecane (cyclen) bearing two semicarbazone pendant groups has been prepared. The octadentate ligand forms complexes with Bi3+ and Pb2+. X-ray crystallography showed that the neutral ligand provides an eight-coordinate environment for both metal ions and intermolecular hydrogen bond interactions have influenced the coordination environments of both complexes in the solid state.

Cardiovascular risk profiles of GnRH agonists and antagonists: real-world analysis from UK general practice.

Purpose: Androgen deprivation therapy (ADT) is the mainstay for the management of metastatic prostate cancer. Available pharmaceutical ADTs include gonadotropin-releasing hormone (GnRH) agonists and antagonists. Here, real-world data are presented from the UK general practitioner Optimum Patient Care Research Database.

Prescription switching: Rationales and risks.

Background: Therapeutic drug switching is commonplace across a broad range of indications and, within a drug class, is often facilitated by the availability of multiple drugs considered equivalent. Such treatment changes are often considered to improve outcomes via better efficacy or fewer side effects, or to be more cost-effective. Drug switching can be both appropriate and beneficial for several reasons; however, switching can also be associated with negative consequences.

Contrast-Induced Encephalopathy following Coronary Angiography with No Radiological Features: A Case Report and Literature Review.

Contrast-induced encephalopathy (CIE) following coronary angiography (CAG) is a very rare complication. Radiological signs such as cerebral oedema and cortical enhancement are of great importance in the diagnosis. We report a case of probable CIE in a 76-year-old gentleman following a normal diagnostic CAG that involved 120 mL of the iodinated contrast agent iohexol (Omnipaque 300).

Inflammatory response to clozapine in the absence of myocarditis: case report.

Summary: A case is presented of a 25-year-old man with treatment-resistant paranoid schizophrenia whose only previous trial of clozapine had been stopped following a suspected clozapine-induced myocarditis. Due to the failure of his psychosis to respond to a number of antipsychotic treatments and augmentation strategies, clozapine was restarted on admission. His rechallenge was marked by intermittent pyrexia, tachycardia and elevated C-reactive protein (CRP), but eosinophilia was absent.

The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK.

Purpose: Comparing gonadotrophin-releasing hormone (GnRH) antagonists and agonists as androgen deprivation therapy for advanced prostate cancer (PC).

Methods: This article stems from a round-table meeting in December 2014 to compare the properties of GnRH agonists and antagonists in the published literature in order to identify the patient groups most likely to benefit from GnRH antagonist therapy. A broad PubMed and congress abstract search was carried out in preparation for the meeting to ensure that the latest data and opinion were available for the discussions.

How to correct the QT interval for the effects of heart rate in clinical studies.

Much inter- and intra-subject variability in the QT interval in health and disease is accounted for by differences in heart rate, leading to difficulties when determining the effects of disease and drugs on the QT interval. Traditionally, heart rate correction formulae have been used to overcome this problem in man. However, the commonly used Bazett's heart rate correction formulae (QT=QT(C) radical RR interval) does not remove the effect of heart rate; indeed, it overcorrects at high heart rates.