Fate of Linear and Branched Polyether-Lipids In Vivo in Comparison to Their Liposomal Formulations by 18F-Radiolabeling and Positron Emission Tomography

In this study, linear poly(ethylene glycol) (PEG) and novel linear-hyperbranched, amphiphilic polyglycerol (hbPG) polymers with cholesterol (Ch) as a lipid anchor moiety were radiolabeled with fluorine-18 via copper-catalyzed click chemistry. In vivo investigations via positron emission tomography (PET) and ex vivo biodistribution in mice were conducted. A systematic comparison to the liposomal formulations with and without the polymers with respect to their initial pharmacokinetic properties during the first hour was carried out, revealing remarkable differences. Additionally, cholesterol was directly labeled with fluorine-18 and examined likewise. Both polymers, Ch-PEG27-CH2-triazole-TEG-…

Back Cover: Macromol. Biosci. 10/2014

Evaluation of [11C]Metergoline as a PET Radiotracer for 5HTR in Nonhuman Primates

Metergoline, a serotonin receptor antagonist, was labeled with carbon-11 in order to evaluate its pharmacokinetics and distribution in non-human primates using positron emission tomography. [{sup 11}C]Metergoline had moderate brain uptake and exhibited heterogeneous specific binding, which was blocked by pretreatment with metergoline and altanserin throughout the cortex. Non-specific binding and insensitivity to changes in synaptic serotonin limit its potential as a PET radiotracer. However, the characterization of [{sup 11}C]metergoline pharmacokinetics and binding in the brain and peripheral organs using PET improves our understanding of metergoline drug pharmacology.

Long-term biodistribution study of HPMA- ran -LMA copolymers in vivo by means of 131 I-labeling

Abstract Background For the evaluation of macromolecular drug delivery systems suitable pre-clinical monitoring of potential nanocarrier systems is needed. In this regard, both short-term as well as long-term in vivo tracking is crucial to understand structure-property relationships of polymer carrier systems and their resulting pharmacokinetic profile. Based on former studies revealing favorable in vivo characteristics for 18 F–labeled random (ran) copolymers consisting of N-(2-hydroxypropyl)methacrylamide (HPMA) and lauryl methacrylate (LMA) – including prolonged plasma half-life as well as enhanced tumor accumulation – the presented work focuses on their long-term investigation in the li…

One-pot, direct incorporation of [11C]CO2 into carbamates.

Why beat about the bush? An operationally simple and mild reaction based on the direct fixation of (11)CO(2) with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) has been developed for the synthesis of (11)C-labeled carbamates at 75 degrees C within 10 minutes in radiochemical yields above 70% (see scheme). This strategy should be immediately useful for the construction of new radiotracers for positron emission tomography and other applications.

18F-Radiolabeling, Preliminary Evaluation of Folate-pHPMA Conjugates via PET

The synthesis of a 10.5 kDa and a 52.5 kDa polymer, based on pHPMA functionalized with tyramine for (18) F-labeling and a folate derivative as targeting moiety, is reported. FCS studies are conducted using Oregon Green-labeled conjugates. No aggregation is observed for the 10.5 kDa conjugate, but strong aggregation for the 52.5 kDa conjugate. In vivo studies are conducted using Walker-256 mammary carcinoma model to determine body distribution as function of size and especially targeting unit. These in vivo studies show a higher short time (2 h) accumulation for both conjugates in the tumor than for untargeted pHPMA, confirmed by blockade studies. The 10.5 kDa polymer accumulates with 0.46% …