Parameter evaluation and fully-automated radiosynthesis of [11C]harmine for imaging of MAO-A for clinical trials

AbstractThe aim of the present study was the evaluation and automation of the radiosynthesis of [11C]harmine for clinical trials. The following parameters have been investigated: amount of base, precursor concentration, solvent, reaction temperature and time. The optimum reaction conditions were determined to be 2–3mg/mL precursor activated with 1eq. 5M NaOH in DMSO, 80°C reaction temperature and 2min reaction time. Under these conditions 6.1±1GBq (51.0±11% based on [11C]CH3I, corrected for decay) of [11C]harmine (n=72) were obtained. The specific activity was 101.32±28.2GBq/µmol (at EOS). All quality control parameters were in accordance with the standards for parenteral human application. Due to its reliability and high yields, this fully-automated synthesis method can be used as routine set-up

Multianalytical study of patina formed on archaeological metal objects from Bliesbruck-Reinheim

Patinas naturally formed on archaeological bronze alloys were characterized using light microscopy (LM), micro energy dispersive X-ray fluorescence analysis (mu-EDXRF), time of flight secondary ion mass spectrometry (TOF-SIMS) and scanning electron microscopy in combination with energy dispersive X-ray microanalysis (SEM/EDX). The examinations carried out on cross-sections of samples have shown that in all samples the copper content in the corrosion layer is lower than in the bulk, while an increase of tin and lead could be observed. Two different types of corrosion were found: first type, a corrosion formation leading to a three layer structure was observed on lead bronze. The outer layer consists mainly of Cu(II) compounds and soil material, followed by a fragmented layer of cuprous oxide and the surface layer of the alloy, where a depletion of copper and an enrichment of tin and high amounts of Cl could be detected, The second type of corrosion is characterized by a two layer structure on the tin bronze sample consisting of an outer layer with copper containing corrosion products and a layer with cracks, which reveals a depletion of copper whereas tin and lead are enriched. Also high amounts of Si were detected in this surface layer

In vivo P-glycoprotein function before and after epilepsy surgery

Objectives: To study the functional activity of the multidrug efflux transporter P-glycoprotein (Pgp) at the blood-brain barrier of patients with temporal lobe epilepsy using (R)-[11C]verapamil (VPM)-PET before and after temporal lobe surgery to assess whether postoperative changes in seizure frequency and antiepileptic drug load are associated with changes in Pgp function. Methods: Seven patients with drug-resistant temporal lobe epilepsy underwent VPM-PET scans pre- and postsurgery. Patients were followed up for a median of 6 years (range 4–7) after surgery. Pgp immunoreactivity in surgically resected hippocampal specimens was determined with immunohistochemistry. Results: Optimal surgical outcome, defined as seizure freedom and withdrawal of antiepileptic drugs, was associated with higher temporal lobe Pgp function before surgery, higher Pgp-positive staining in surgically resected hippocampal specimens, and reduction in global Pgp function postoperatively, compared with nonoptimal surgery outcome. Conclusions: The data from our pilot study suggest that Pgp overactivity in epilepsy is dynamic, and complete seizure control and elimination of antiepileptic medication is associated with reversal of overactivity, although these findings will require confirmation in a larger patient cohort

Cyclotrons Operated for Nuclear Medicine and Radiopharmacy in the German Speaking D-A-CH Countries: An Update on Current Status and Trends

Background: Cyclotrons form a central infrastructure and are a resource of medical radionuclides for the development of new radiotracers as well as the production and supply of clinically established radiopharmaceuticals for patient care in nuclear medicine. Aim: To provide an updated overview of the number and characteristics of cyclotrons that are currently in use within radiopharmaceutical sciences and for the development of radiopharmaceuticals to be used for patient care in Nuclear Medicine in Germany (D), Austria (A) and Switzerland (CH). Methods: Publicly available information on the cyclotron infrastructure was (i) consolidated and updated, (ii) supplemented by selective desktop research and, last but not least, (iii) validated by members of the committee of the academic “Working Group Radiochemistry and Radiopharmacy” (AGRR), consisting of radiochemists and radiopharmacists of the D-A-CH countries and belonging to the German Society of Nuclear Medicine (DGN), as well as the Radiopharmaceuticals Committee of the DGN. Results: In total, 42 cyclotrons were identified that are currently being operated for medical radionuclide production for imaging and therapy in Nuclear Medicine clinics, 32 of them in Germany, 4 in Austria and 6 in Switzerland. Two thirds of the cyclotrons reported (67%) are operated by universities, university hospitals or research institutions close to a university hospital, less by/in cooperation with industrial partners (29%) or a non-academic clinic/ PET-center (5%). Most of the cyclotrons (88%) are running with up to 18 MeV proton beams, which is sufficient for the production of the currently most common cyclotron-based radionuclides for PET imaging. Discussion: The data presented provide an academically-updated overview of the medical cyclotrons operated for the production of radiopharmaceuticals and their use in Nuclear Medicine in the D-A-CH countries. In this context, we discuss current developments and trends with a view to the cyclotron infrastructure in these countries, with a specific focus on organizational aspects

Preclinical In Vitro

Molecular imaging probes such as PET-tracers have the potential to improve the accuracy of tumor characterization by directly visualizing the biochemical situation. Thus, molecular changes can be detected early before morphological manifestation. The A3 adenosine receptor (A3AR) is described to be highly expressed in colon cancer cell lines and human colorectal cancer (CRC), suggesting this receptor as a tumor marker. The aim of this preclinical study was the evaluation of [F]FE@SUPPY as a PET-tracer for CRC using in vitro imaging and in vivo PET imaging. First, affinity and selectivity of FE@SUPPY and its metabolites were determined, proving the favorable binding profile of FE@SUPPY. The human adenocarcinoma cell line HT-29 was characterized regarding its hA3AR expression and was subsequently chosen as tumor graft. Promising results regarding the potential of [F]FE@SUPPY as a PET-tracer for CRC imaging were obtained by autoradiography as 2.3-fold higher accumulation of [F]FE@SUPPY was found in CRC tissue compared to adjacent healthy colon tissue from the same patient. Nevertheless, first in vivo studies using HT-29 xenografts showed insufficient tumor uptake due to (1) poor conservation of target expression in xenografts and (2) unfavorable pharmacokinetics of [F]FE@SUPPY in mice. We therefore conclude that HT-29 xenografts are not adequate to visualize hA3ARs using [F]FE@SUPPY.(VLID)481541

Introduction to Different PET Radiopharmaceuticals and Hybrid Modalities (PET/CT and PET/MRI)

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