Exametazime (stabilised) 500microgram kit for radiopharmaceutical preparation

The synthesis of radiopharmaceuticals is a major task of nuclear medicine, and Technetium-99m (99mTc) has ideal nuclear properties for non-invasive nuclear medical diagnostics by single-photon emission computed tomography (SPECT) – a cheaper method than CT, MRI, and PET, suitable for developing countries. Of particular relevance today is the design of various covalently labelled 99mTc radiopharmaceuticals for the diagnosis and theranostics of oncological diseases. However, the correct selection of ligands and the development of high-quality 99mTc-based imaging agents that will not disrupt the functions of biologically active molecules requires a good understanding of the coordination chemistry of group 7 transition metals. In this work, the quantum-chemical characteristics of ten 99mTc radiopharmaceuticals were calculated using ab initio (a combined basis set: SBKJC on the Tc atom and 6-31G (d,p)/DFT – on other atoms, Gamess) and semi-empirical (PM6, MOPAC) methods. Negative (for Tc-Exametazime, Tc-ECD) and positive (for other 99mTc complexes) values of the ЕLUMO parameter indicated the electrophilic and nucleophilic properties of the radiopharmaceuticals, respectively. Analysis of the absolute hardness values of the complexes revealed that the studied radiopharmaceuticals are soft reagents, with Pertechnetate having the lowest reactivity, which is consistent with the literature data. Dipole moments of most of the 99mTc radiopharmaceuticals were similar or up to one order of magnitude greater as compared to that of a water molecule. Finally, a strong correlation was established between the ground state dipole moments, lipophilicity and the percentage of nonspecific binding of five radiopharmaceuticals (Tc-Exametazime, Tc-MAG3, Tc-MDP, Tc(III)-DMSA, Tc-DTPA) to plasma proteins (Pearson’s correlation coefficients were ca. -0.719 and 0.611, respectively). The obtained results could be employed for the design of new 99mTc-based theranostic agents suitable for cancer treatment, in particular those with high nonspecific binding to plasma proteins.

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En esta guía se describe el procedimiento radiofarmacéutico de preparación de leucocitos marcados in vitro . La gammagrafía con leucocitos marcados con [ 99m Tc]Tc-exametazima o [ 111 In]In-oxina es una prueba diagnóstica de gran utilidad en enfermedades infecciosas e inflamatorias debido a su elevada sensibilidad y especificidad. Basándonos en las guías y protocolos consensuados, a los que se han incorporado las directrices de la reciente regulación de la preparación extemporánea de radiofármacos en España, esta guía proporciona instrucciones detalladas y precisas para una segura y eficaz preparación y control de calidad de los leucocitos marcados in vitro . Se detallan las indicaciones clínicas de la gammagrafía con leucocitos marcados y se describen los requerimientos técnicos tanto de las instalaciones como del equipamiento necesario. Se desarrollan y se fundamentan las diferentes etapas que comprenden el procedimiento de radiomarcaje, desde la obtención de la muestra sanguínea, la separación y el aislamiento de la fracción leucocitaria, la incubación y consiguiente marcaje radioisotópico tanto con [ 99m Tc]Tc-exametazima como con [ 111 In]In-oxina, el acondicionamiento del radiofármaco para su administración, así como los controles de calidad necesarios. El documento concluye con un apartado donde se describen las interacciones medicamentosas descritas en la literatura. Se incluyen 2 anexos con ejemplos de protocolos de marcaje para ambos radiofármacos. This guide outlines the radiopharmaceutical procedure for the in vitro labelling of leukocytes. Scintigraphy using leukocytes labeled with [ 99m Tc]Tc-exametazime or [ 111 In]In-oxine is a highly valuable diagnostic tool in infectious and inflammatory diseases due to its high sensitivity and specificity. It is based on established guidelines and consensus protocols, which incorporate the recent Spanish regulations on the extemporaneous preparation of radiopharmaceuticals, this document provides detailed and precise instructions for the safe and effective preparation and quality control of in vitro labeled leukocytes. The clinical indications for leukocyte scintigraphy are described, along with the technical requirements for both facilities and equipment. The various stages of the radiolabelling procedure are developed and substantiated, including blood sample collection, leukocyte fraction separation and isolation, incubation and subsequent radiolabelling with either [ 99m Tc]Tc-exametazime or [ 111 In]In-oxine, radiopharmaceutical conditioning for administration, and the necessary quality control procedures. The document concludes with a section describing drug interactions reported in the literature. Two annexes are included, providing example labeling protocols for both radiopharmaceuticals.

Abstract licence: CC BY-NC-ND

Certain foods and specific drugs have been linked to epilepsy in the literature. Here, we query PubMed citations for the co-occurrence of epilepsy with foods and drugs, using a list of 217,776 molecules from the HMDB. Notably, the top associations with epilepsy include approved drugs and drug families, diagnostic markers, inducers, and vitamins. Drugs include fosphenytoin (40%), topiramate (37%), valproic acid (34%), hydantoin (20%), phenytoin (31%), carbamazepine (33%), carbamazepine-10,11-epoxide (40%), trimethadione (31%), gabapentin (14%), pregabalin (11%), flunarizine (7%), fenfluramine (4%), bumetanide (4%), KBr (18%), cannabidiol (14%), clonazepam (22%), nitrazepam (10%), diazepam (7%), lorazepam (6%), midazolam (3%), amobarbital (21%), phenobarbital (16%), flumazenil (7%) allopregnanolone (7%), pregnanolone (6%), epipregnanolone (6%), 3-hydroxypregnan-20-one (6%), and vitamin B6 (6%). Drug families and scaffolds include imidazolidine (18%), succinimide (10%), acetamide (7%), 2-pyrrolidinone (7%), pyrrolidine (6%), tetrahydropyridine (6%), and isoxazole (4%). Investigational compounds include cyano-7-nitroquinoxaline-2,3-dione (5%). Diagnostic markers include exametazime (10%) and quinolinic acid (3%). Inducers include flurothyl (37%), pentetrazol (32%), pilocarpine (25%), (+)-Bicuculline (8%), and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP, 6%). Our analysis highlights frequently cited associations between epilepsy and specific drugs and highlights the importance of supplementing nutrients with vitamin B6 and the ketogenic diet, which increases the gamma-aminobutyric acid (GABA)/glutamate ratio. As such, our study offers dietary approaches in the treatment of this neurodegenerative disease.

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Abstract Background Cholinergic dysfunction, particularly involving nicotinic acetylcholine receptors (nAChRs), contributes to cognitive and psychiatric symptoms in dementia with Lewy bodies (DLB), yet spatial covariance patterns remain unexplored. We aimed to characterise these patterns using 123 I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) SPECT (α4β2 nAChR assessment) and examine their association with cognitive function. Methods Fifteen DLB and 16 healthy controls underwent 123 5IA-85380 and rCBF 99m Tc-exametazime SPECT scanning. Voxel principal components analysis (PCA), generated PC images representing common intercorrelated voxels across subjects. Linear regression identified α4β2 nAChR and rCBF patterns distinguishing DLB from controls. Results A distinct α4β2 nAChR pattern differentiated DLB from controls (F 1,29 = 165.1, p < 0.001), that was dissimilar to rCBF changes. This pattern was characterised by decreased uptake in temporal pole, inferior frontal cortex, amygdala, olfactory cortex, insula, anterior/mid cingulate, and putamen, alongside preserved/increased uptake in sensorimotor cortex, fusiform and occipital lobe. These regions mapped onto default, salience, limbic, frontostriatal, sensorimotor and visual hubs. We then derived from patients, α4β2 nAChR patterns that correlated with CAMCOG total ( r = – 0.52, p = 0.04), MMSE ( r = – 0.68, p = 0.01) and CAMCOG memory ( r = – 0.70, p = 0.01), demonstrating a common topography of relative decreased binding in lateral/medial prefrontal, lateral temporal, fusiform, inferior parietal and thalamus along with relative preserved/increased binding in cingulate, insula, occipital and medial temporal regions: structures within a range of networks supporting executive, language, attention, motor and visual processing. Conclusion These findings provide novel insights into the pathophysiology of DLB and may inform future therapeutic strategies targeting nAChRs.

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