18F-labelled CCR1-receptor antagonist is not suitable for imaging of Alzheimer's disease.

Diagnosis of Alzheimer's disease (AD) with positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) relies on typical alterations of brain glucose metabolism which are, however, not disease specific. Amyloid-ß imaging has not entered clinical routine yet. Post mortem histological specimen of brain tissue from AD patients revealed enhanced expression of the chemotactic cytocine receptor 1 (CCR1). PARTICIPANTS, METHODS: CCR1-antagonist ZK811460 was labeled with fluorine-18 to explore its possible use as specific diagnostic tool in AD. Tracer characterization comprising PET imaging of brain and metabolite analysis was performed in AD patients and controls. RESULTS: Neither qualitative evaluation nor quantitative compartment analysis of PET data did show any enhanced binding of the 18F-labeled CCR1-antagonist in the brain of AD patients or controls. CONCLUSION: 18F-ZK811460 did not fulfill the expectation as diagnostic tracer in PET imaging of AD.

Module-assisted preparation of 64Cu with high specific activity.

In this work the production of (64)Cu via the (64)Ni(p,n)(64)Cu reaction with optimized conditions for low current irradiation is presented. Different target setups and cleaning steps for lowering metal contaminations in the product were applied. (64)Cu with high specific activities up to 1685 GBq/µmol was produced despite low overall activity (≈ 4.2 GBq per run). The module processing leads to a highly reproducible, reliable product quality (<1 µg Cu and <7 µg Ni). Besides its diagnostic value (64)Cu may be of interest even for therapeutic purposes due to its decay characteristics.

Factors affecting the specific activity of [18F]fluoride from a [18O]water target.

AIM: Characterisation of the influence of different polymeric tube materials of a water target system, used for the production of 18F activity, on the specific activity of radiotracers. MATERIAL, METHODS: Target water samples taken from different locations of the 18F water target system of a Cyclone 18/9 cyclotron, equipped with Teflon (PTFE) or polypropylene (PP) tubes, were analyzed for non-radioactive [19F]fluoride content. [19F]Fluoride content was measured by ion chromatography (IC20, Dinoex) with suppressed conductivity detection. Both the ion chromatographic results and the amount of 18F activity produced were used for the calculation of the specific activity (SA) of [18F]fluoride at the start of the labelling synthesis. To check these results, the SA of the labelled receptor ligand [18F]ZK811460 was also determined by using the different tubing materials. RESULTS: Dose-exposed PTFE tubes of the target dispensing (loading) system were identified to be a major source of [19F]fluoride contamination. CONCLUSION: By replacing PTFE tubes of the target dispensing system with PP tubes, the content of 19F was reduced considerably resulting in an increase of SA of the radiotracer [18F]ZK811460 by factor of two.

Aspects of 6-[18F]fluoro-L-DOPA preparation. Deuterochloroform as a substitute solvent for Freon 11.

AIM: Replacement of the ecologically harmful solvent Freon 11 (CFCl(3)) by chloroform for the module-assisted preparation of 6-[(18)F]fluoro-L-DOPA based on the electrophilic radiofluorodestannylation of the precursor N-formyl-3,4-di-tert-butoxycarbonyloxy-6-(trimethylstannyl)-L-phenylalanine ethyl ester. MATERIALS, METHODS: The TRACERlab Fx FDOPA module (GE Medical Systems) was used for the preparation of 6-[(18)F]fluoro-L-DOPA. Cyclotron-produced [(18)F]F(2) gas (5 GBq) was passed through a cooled solution (5 degrees C) of the stannyl precursor (45 mg) in CDCl(3) (10 ml). After the [(18)F]fluorination step, HCl (2 ml, 6 mol/l) was added to the solution. Then the reaction mixture was heated at 80 degrees C for 5 min under vacuum to evaporate the chloroform. The hydrolysis to remove the protecting groups was completed by heating the closed reactor at 130 degrees C for 8 min. After cooling to 20 degrees C the reaction mixture was purified by HPLC with two polymer-based RP columns (PRP-1, 7 microm, 10 x 250 mm, Hamilton) using a solution of AcOH/AcONa (pH 4.7) as eluent. The 6-[(18)F]fluoro-L-DOPA fraction was collected and sterile filtrated. RESULTS: Three types of stabilised chloroform were tested for the radiofluorination of the precursor. Only by use of deuterochloroform stabilised with silver no significant losses of radioactivity were observed. Thus, 6-[(18)F]fluoro-L-DOPA purified by HPLC was obtained in decay-corrected radiochemical yields of 25+/-3%, ready for human use. CONCLUSION: CDCl(3) has proved to be a convenient solvent for the module-assisted preparation of 6-[(18)F]fluoro-L-DOPA. In this way the use of the polluting Freon 11 can be avoided.

Module-assisted synthesis of the bifunctional labelling agent N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB).

The three-step radiosynthesis of N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB) was adapted to a remotely controlled synthesis module. After optimization of the reaction conditions, the final [(18)F]SFB was obtained in decay-corrected radiochemical yields of 34-38% (related to [(18)F]fluoride; n=12) within a synthesis time of 68 min. The radiochemical purity was in the range of 93-96%.

Radio fluorination and positron emission tomography (PET) as a new approach to study the in vivo distribution and elimination of the advanced glycation endproducts N epsilon-carboxymethyllysine (CML) and N epsilon-carboxyethyllysine (CEL).

After synthesis of fluorine-18 labelled analogues by [18F]fluorobenzoylation at the alpha-amino group, biodistribution and elimination of individual advanced glycation endproducts, namely N epsilon-carboxymethyllysine and N epsilon-carboxyethyllysine, were studied in comparison to lysine in rats after intravenous injection using positron emission tomography (PET). The [18F]radiofluorinated amino acids were fast distributed via the blood, followed by a rapid excretion through the kidneys. Elimination kinetics were similar for both AGEs and lysine. For CML and CEL, but not for lysine, a temporary liver accumulation could be observed, which was not connected with any metabolisation or enterohepatic circulation. No further accumulation in any tissues was observable, indicating that increased tissue levels of CML or CEL, which have been described for certain disorders, are exclusively derived from endogenous origin and should not depend on a dietary intake. However, under uremic conditions, an impaired kidney function might result in a significant increase of the AGE-load of blood and tissues. PET based on 18F-labelled AGEs proved to be a promising tool to elucidate the physiological fate of post-translationally modified amino acids and to clarify the role of AGEs as possible "glycotoxins".

[The effect of ethylenediaminetetramethylenephosphonate on the biodistribution of tumor-seeking radionuclides]. / Der Einfluss von Ethylendiamintetramethylenphosphonat auf die Bioverteilung tumoraffiner Radionuklide.

It is well known that after application of radioactive complexes for tumour diagnosis or therapy, such as 67Ga-citrate or radiolanthanide complexes (167Tm- or 169Yb-nitrilotriacetate, -citrate, -alpha-hydroxyisobutyrate, 90Y-citrate, etc.) activity is accumulated not only in the tumour but also in other organs, above all liver and bone. This is the main obstacle to their medical use. Recently published results encouraged us to use ethylenediaminetetramethylene phosphonate (EDTMP) for the reduction of extratumoural liver activity. The results show that even small amounts of EDTMP (1-2 mg/kg BW) reduce the activity deposition in the liver by about one order of magnitude. EDTMP provoked elimination of activity from tumour, skeleton and other tissues but not to the same extent as from the liver. Tumor/liver activity ratios > 5 are achievable in this manner.

Simultaneous study of the biodistribution of radio-yttrium complexed with EDTMP and citrate ligands in tumour-bearing rats.

The influence of the ligands ethylenediaminetetramethylene phosphonic acid (EDTMP) and citrate (CIT) on the biodistribution of radio-yttrium in rats bearing a DS-carcinosarcoma was compared. 88Y-EDTMP and 87Y-CIT were i.v. injected into the same animals. Faster blood clearance and higher renal excretion were observed for the EDTMP-ligand. Of high practical interest is the reduced liver uptake of radio-yttrium (by one order of magnitude) with the EDTMP complex. Since bone and tumour accumulation is only weakly influenced, high tumour-to-liver ratios (up to 14) were observed. We propose to use EDTMP or similar complex ligands for liver blocking when radionuclides like 90Y, 169Yb, 225Ac or other group 3 elements are to be applied in endoradionuclide therapy technique.

Preparation of [99mTc(DMPE)2Cl2]+ for myocardial imaging by using Fe-(DMPE) complexes.

The preparation of [99mTc(1,2-bis(dimethylphosphino)ethane)2Cl2]+ ([99mTc(DMPE)2Cl2]+) for imaging the myocardium is investigated. Starting from Fe(III)- or Fe(II)-DMPE and 99mTcO4- different preparation variants are compared. In these reactions either ascorbic acid or DTPA serves as an agent for complexing iron. A simple procedure using lyophilized initial components is represented. Its application yields [99mTc(DMPE)2Cl2]+ with a radiochemical purity of more than 95%. Organ distribution studies performed in rats emphasize the high myocardial accumulation of this preparation.