0000000000409612
AUTHOR
Markus Jahn
Radioactive labeling of defined HPMA-based polymeric structures using [18F]FETos for in vivo imaging by positron emission tomography.
During the last decades polymer-based nanomedicine has turned out to be a promising tool in modern pharmaceutics. The following article describes the synthesis of well-defined random and block copolymers by RAFT polymerization with potential medical application. The polymers have been labeled with the positron-emitting nuclide fluorine-18. The polymeric structures are based on the biocompatible N-(2-hydroxypropyl)-methacrylamide (HPMA). To achieve these structures, functional reactive ester polymers with a molecular weight within the range of 25,000-110,000 g/mol were aminolyzed by 2-hydroxypropylamine and tyramine (3%) to form (18)F-labelable HPMA-polymer precursors. The labeling procedure…
Processing of Generator-Produced 68Ga for Medical Application
The (68)Ge/(68)Ga generator provides an excellent source of positron-emitting (68)Ga. However, newly available "ionic" (68)Ge/(68)Ga radionuclide generators are not necessarily optimized for the synthesis of (68)Ga-labeled radiopharmaceuticals. The eluates have rather large volumes, a high concentration of H(+) (pH of 1), a breakthrough of (68)Ge, increasing with time or frequency of use, and impurities such as stable Zn(II) generated by the decay of (68)Ga, Ti(IV) as a constituent of the column material, and Fe(III) as a general impurity.We have developed an efficient route for the processing of generator-derived (68)Ga eluates, including the labeling and purification of biomolecules. Prec…
72/74As-labeling of HPMA based polymers for long-term in vivo PET imaging
Abstract In the context of molecular imaging, various polymers based on the clinically approved N-(2-hydroxypropyl)-methacrylamide (HPMA) have been radio-labeled using longer-living positron emitters 72As t1/2 = 26 h or 74As t1/2 = 17.8 d. This approach may lead to non-invasive determination of the long-term in vivo fate of polymers by PET (positron emission tomography). Presumably, the radio label itself will not strongly influence the polymer structure due to the fact that the used nuclide binds to already existing thiol moieties within the polymer structure. Thus, the use of additional charges or bulky groups can be avoided.
Hemin-coupled iron(III)-hydroxide nanoparticles show increased uptake in Caco-2 cells
Abstract Objectives The absorption of commonly used ferrous iron salts from intestinal segments at neutral to slightly alkaline pH is low, mainly because soluble ferrous iron is easily oxidized to poorly soluble ferric iron and ferrous iron but not ferric iron is carried by the divalent metal transporter DMT-1. Moreover, ferrous iron frequently causes gastrointestinal side effects. In iron(III)-hydroxide nanoparticles hundreds of ferric iron atoms are safely packed in nanoscaled cores surrounded by a solubilising carbohydrate shell, yet bioavailability from such particles is insufficient when compared with ferrous salts. To increase their intestinal uptake iron(III)-hydroxide nanoparticles …
Iron Oxide/Hydroxide Nanoparticles with Negatively Charged Shells Show Increased Uptake in Caco-2 Cells
The absorption of commonly used ferrous iron salts from intestinal segments at neutral to slightly alkaline pH is low, mainly because soluble ferrous iron is easily oxidized to poorly soluble ferric iron and because ferrous iron, but not ferric iron, is carried by the divalent metal transporter DMT-1. Moreover, ferrous iron frequently causes gastrointestinal side effects. Iron hydroxide nanoparticles with neutral and hydrophilic carbohydrate shells are alternatively used to ferrous salts. In these formulations gastrointestinal side effects are rare because hundreds of ferric iron atoms are safely packed in nanoscaled cores surrounded by the solubilizing shell; nevertheless, iron bioavailabi…
CE characterization of potential toxic labile iron in colloidal parenteral iron formulations using off-capillary and on-capillary complexation with EDTA.
The present study describes the application of CZE to investigate the portion of labile iron in the following parenteral formulations: iron gluconate, iron saccharate, and iron dextran. Labile iron was detected as Fe(III)-chelate of EDTA at 246 nm. When EDTA was incubated with the formulations before electrophoresis, labile iron, or chelatable iron, respectively, was detected in all formulations, mostly in iron gluconate and iron saccharate. It was observed that the amount of iron released is time- and pH-dependent. In contrast, when EDTA was separately injected before the formulation sharp peaks of the Fe(III)-chelate were detected only after injection of iron gluconate. This type of labil…
Separation and purification of no-carrier-added arsenic from bulk amounts of germanium for use in radiopharmaceutical labelling
AbstractRadioarsenic labelled radiopharmaceuticals could add special features to molecular imaging with positron emission tomography (PET). For example the long physical half-lives of72As (T1/2=26 h) and74As (T1/2=17.8 d) in conjunction with their high positron branching rates of 88% and 29%, respectively, allow the investigation of slow physiological or metabolical processes, like the enrichment and biodistribution of monoclonal antibodies in tumour tissue or the characterization of stem cell trafficking. A method for separation and purification of no-carrier-added (nca) arsenic from irradiated metallic germanium targets based on distillation and anion exchange is developed. It finally con…
A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer®), a new intravenous iron preparation and its clinical implications
Abstract The treatment of iron deficiency anemia with polynuclear iron formulations is an established therapy in patients with chronic kidney disease but also in other disease areas like gastroenterology, cardiology, oncology, pre/post operatively and obstetrics’ and gynecology. Parenteral iron formulations represent colloidal systems in the lower nanometer size range which have traditionally been shown to consist of an iron core surrounded by a carbohydrate shell. In this publication, we for the first time describe the novel matrix structure of iron isomaltoside 1000 which differs from the traditional picture of an iron core surrounded by a carbohydrate. Despite some structural similaritie…
A new method for radiochemical separation of arsenic from irradiated germanium oxide.
Abstract Radioarsenic labelled radiopharmaceuticals could be a valuable asset to Positron Emission Tomography (PET). In particular, the long half-lives of 72 As ( T 1/2 =26 h) and 74 As ( T 1/2 =17.8 d) allow to investigate slow physiological or metabolical processes, like the enrichment and distribution of antibodies in tumor tissue. This work describes the direct production of no-carrier-added (nca) arsenic isotopes *As, with *=71, 72, 73, 74 or 77, the reaction to [*As]AsI 3 and its radiochemical separation from the irradiated solid germanium oxide via polystyrene-based solid-phase extraction. The germanium oxide target, irradiated at a cyclotron or a nuclear reactor, is dissolved in con…