Improved synthesis of [18F] fallypride and characterization of a Huntington’s disease mouse model, zQ175DN KI, using longitudinal PET imaging of D2/D3 receptors

Dopamine receptors are involved in pathophysiology of neuropsychiatric diseases, including Huntington’s disease (HD). PET imaging of dopamine D2 receptors (D2R) in HD patients has demonstrated 40% decrease in D2R binding in striatum, and D2R could be a reliable quantitative target to monitor disease progression. A D2/3R antagonist, [18F] fallypride, is a high-affinity radioligand that has been clinically used to study receptor density and occupancy in neuropsychiatric disorders. Here we report an improved synthesis method for [18F]fallypride. In addition, high molar activity of the ligand has allowed us to apply PET imaging to characterize D2/D3 receptor density in striatum of the recently developed zQ175DN knock-in (KI) mouse model of HD.Peer reviewe

Native and Complexed IGF-1: Biodistribution and Pharmacokinetics in Infantile Neuronal Ceroid Lipofuscinosis

Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disorder of childhood characterized by selective death of cortical neurons. Insulin-like growth factor 1 (IGF-1) is important in embryonic development and is considered as a potential therapeutic agent for several disorders of peripheral and central nervous systems. In circulation IGF-1 is mainly bound to its carrier protein IGFBP-3. As a therapeutic agent IGF-1 has shown to be more active as free than complexed form. However, this may cause side effects during the prolonged treatment. In addition to IGFBP-3 the bioavailability of IGF-1 can be modulated by using mesoporous silicon nanoparticles (NPs) which are optimal carriers for sustained release of unstable peptide hormones like IGF-1. In this study we compared biodistribution, pharmacokinetics, and bioavailability of radiolabeled free IGF-1, IGF-1/IGFBP-3, and IGF-1/NP complexes in a Cln1-/- knockout mouse model. IGF-1/NP was mainly accumulated in liver and spleen in all studied time points, whereas minor and more constant amounts were measured in other organs compared to free IGF-1 or IGF-1/IGFBP-3. Also concentration of IGF-1/NP in blood was relatively high and stable during studied time points suggesting continuous release of IGF-1 from the particles

Sylkirauhasten ohutneulanäytteille Milanon luokitus

Sylkirauhasen ohutneulanäytteiden uusi luokitus tarkentaa sytologisia kriteereitä ja antaa hoidon tai seurannan kannalta olennaista tietoa hoitavaan yksikköön. Vastauskäytännöt on sovittava kliinikoiden kanss

Porous Silicon Particles for Cancer Therapy and Bioimaging

Porous silicon (pSi) engineered by electrochemical etching of silicon has been explored as a drug delivery carrier with the aim of overcoming the limitations of traditional therapies and medical treatments. pSi is biodegradable, non-cytotoxic and has optoelectronic properties that make this platform material a unique candidate for developing biomaterials for drug delivery and theranostics therapies. pSi provides new opportunities to improve existing therapies in different areas, paving the way for developing advanced theranostic nanomedicines, incorporating payloads of therapeutics with imaging capabilities. However, despite these outstanding advances, more extensive in-vivo studies are needed to assess the feasibility and reliability of this technology for real clinical practice. In this Chapter, we present an updated overview about the recent therapeutic systems based on pSi, with a critical analysis on the problems and opportunities that this technology faces as well as highlighting the growing potential of pSi technolgy