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Unnatural mirror image l-configured oligonucleotides (L-ONs) are a convenient substance class for the application as complementary in vivo recognition system between a tumor specific antibody and a smaller radiolabeled effector molecule in pretargeting approaches. The high hybridization velocity and defined melting conditions are excellent preconditions of the L-ON based methodology. Their high metabolic stability and negligible unspecific binding to endogenous targets are superior characteristics in comparison to their d-configured analogs. In this study, a radiopharmacological evaluation of a new l-ONs based pretargeting system using the epidermal growth factor receptor (EGFR) specific antibody cetuximab (C225) as target-seeking component is presented. An optimized PEGylated 17mer-L-DNA was conjugated with p-SCN-Bn-NOTA (NOTA′) to permit radiolabeling with the radionuclide 64Cu. C225 was modified with the complementary 17mer-L-DNA (c-L-DNA) strand as well as with NOTA′ for radiolabeling and use for posi...

Technetium-labeled fatty acids intended for myocardial metabolism imaging and the respective rhenium model complexes were synthesized according to the "4 + 1" mixed-ligand approach and investigated in vitro and in vivo. The non-radioactive rhenium model complexes were characterized by NMR, IR, and EA, and the geometrical impact of the chelate unit on the integrity of the fatty acid head structure was determined by single-crystal X-ray analyses. To estimate the diagnostic value of the 99mTc-labeled fatty acids, the compounds were investigated in experiments in vitro and in biodistribution studies using male Wistar rats. The new fatty acid tracers contain the metal core in the oxidation states +3, well-wrapped in a trigonal-bipyramidal coordination moiety, which is attached at the omega-position of a fatty acid chain. This structural feature is considered to be a good imitation of the well-established iodinated phenyl fatty acids. High heart extraction in perfused heart studies (up to 26% injected dose (ID)) and noticeable heart uptake of the 99mTc tracers in vivo being in the order of 2% ID/g at 5 min (postinjection, pi.), accompanied by a good heart to blood ratio of 8, confirms that the new Tc compounds are suitable as fatty acid tracers.

2-[18F]Fluoro-2-deoxy-D-glucose ([18F]FDG) as the most important PET radiotracer is available in almost every PET center. However, there are only very few examples using [18F]FDG as a building block for the synthesis of 18F-labeled compounds. The present study describes the use of [18F]FDG as building block for the synthesis of 18F-labeled peptides and proteins. [18F]FDG was converted into [18F]FDG-maleimidehexyloxime ([18F]FDG-MHO), a novel [18F]FDG-based prosthetic group for the mild and thiol group-specific 18F labeling of peptides and proteins. The reaction was performed at 100°C for 15 min in a sealed vial containing [18F]FDG and N-(6-aminoxy-hexyl)maleimide in 80% ethanol. [18F]FDG-MHO was obtained in 45-69% radiochemical yield (based upon [18F]FDG) after HPLC purification in a total synthesis time of 45 min. Chemoselecetive conjugation of [18F]FDG-MHO to thiol groups was investigated by the reaction with the tripeptide glutathione (GSH) and the single cysteine containing protein annexin A5 (anxA5). Radiolabeled annexin A5 ([18F]FDG-MHO-anxA5) was obtained in 43-58% radiochemical yield (based upon [18F]FDG-MHO, n=6), and [18F]FDG-MHO-anxA5 was used for a pilot small animal PET study to assess in vivo biodistribution and kinetics in a HT-29 murine xenograft model.

Our group previously synthesized 99m Tc-labeled fatty acids suitable for myocardial metabolism and flow imaging. In this set of experiments, 29 new analogues were synthesized according to the "4 + 1" mixed ligand approach with some specific differences. Conventional "4 + 1" 99m Tc-fatty acids are built in the sequence: Tc-chelate, alkyl chain, and carboxylic group. We developed compounds following a new design with the sequence: carboxylic group, alkyl chain, Tc-chelate, and lipophilic tail. Therefore, the 99m Tc-chelate was transferred to a more central position of the compound, aiming toward an improved myocardial profile and an accelerated liver clearance. In this context, several functional groups incorporated in the lipophilic tail section were tested to evaluate their influence on the compound's character. In addition to biodistribution studies in vivo, the myocardial first-pass extraction of the compounds was tested in an isolated Langendorff rat heart model. A satisfactory myocardial uptake of up to 20% of the injected dose (% ID) in the perfused heart and a fast liver clearance in vivo with only 0.29% ID/g at 60 min postinjection demonstrate that the induced molecular modifications affect the kinetics of 99m Tc-radiolabeled fatty acid compounds favorably. From the data set, rules for estimating the biodistribution of fatty acids tracers are deduced.