Copper-free click bioconjugation of technetium-99m complexes using strained cyclononyne derivatives.

Click chemistry, in particular copper-free click reactions, has gained growing interest for radiolabelling purposes in the field of radiopharmaceutical sciences. [Tc][Tc(CO)(HO)] works as an excellent starting complex for the radiolabelling of biomolecules under mild conditions. A new chelator, investigated for the copper-free strain-promoted cycloaddition (SPAAC), was synthesised containing the 2,2'-dipicolylamine (DPA) moiety for the Tc-tricarbonyl core and compared with a DPA chelator based on activated esters for conventional radiolabelling.

Strategic Evaluation of the Traceless Staudinger Ligation for Radiolabeling with the Tricarbonyl Core.

The traceless Staudinger ligation with its two variants is a powerful biorthogonal conjugation method not only for the connection of biomolecules, but also for the introduction of fluorescence- or radiolabels under mild reaction conditions. Herein, the strategic evaluation of the traceless Staudinger ligation for radiolabeling Tc using the -[Tc(CO)] core is presented. A convenient and high-yielding three-step synthetic procedure of dipicolylamine-based phosphanols as ligands for the mild radiolabeling was developed.

Assessment of the best N(3-) donors in preparation of [M(N)(PNP)]-based (M=(99m)Tc-; (188)Re) target-specific radiopharmaceuticals: Comparison among succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ).

Succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ) are nitrido nitrogen atom donors employed for the preparation of nitride [M(N)]-complexes (M=(99m)Tc and (188)Re). This study aims to compare the capability and the efficiency of these three N(3-) group donors, in the preparation of [M(N)PNP]-based target-specific compounds (M=(99m)Tc, (188)Re; PNP=aminodiphosphine). For this purpose, three different kit formulations (SDH kit; HO2C-PEG600-DTCZ kit; HDTCZ kit) were assembled and used in the preparation of [M(N)(cys~)(PNP3)](0/+) complexes (cys~=cysteine derivate ligands).

Design and development of (99m)tc-'4+1'-labeled dextran-mannose derivatives as potential radiopharmaceuticals for sentinel lymph node detection.

The synthesis, labeling, and biological evaluation of a dextran derivative (DCM-30-iso) as potential radiopharmaceutical for sentinel lymph node imaging is presented. DCM-30-iso bears mannose as active moiety and isocyanide as ligand for technetium through the formation of a '4+1' Tc(III) mixed-ligand complex. A second derivative without mannose (DC-25-iso) was also prepared and evaluated as control.

Very stable 188Re-S4 chelates for labelling biomolecules: preparation with highly concentrated perrhenate eluates.

Aim: The preparation and stability of a new (188)Re-S(4)-complex [S(4) = (1-aza-18-crown-6)(O)C-C(SH)-C(SH)-C(O)NH-(CH(2))(3)-NH-(CH(2))(3)-NHC(O)-C(SH)-C(SH)-C(O)(1-aza-18-crown-6] was studied at therapeutic relevant radioactive concentrations. The results were compared with (188)Re-MAG(3) (MAG(3): mercaptoacetyltriglycine) and (188)Re-DMSA preparations (DMSA: dimercaptosuccinic acid) performed with the same highly concentrated [(188)Re]perrhenate solution (12-15 GBq/ml).

Methods: The (188)Re complexes were prepared by direct reduction of perrhenate ((188)Re-S(4)-complex) as well as via the (188)Re-EDTA precursor complex ((188)Re-MAG(3), (188)Re-DMSA).

Preparation and biological characterization of isomeric 188Re(V) oxocomplexes with tetradentate S4 ligands derived from meso-dimercaptosuccinic acid for labeling of biomolecules.

A new type of tetradentate S4 ligand has been synthesized by bridging two molecules of meso-2,3-dimercaptosuccinic acid for stable binding and easy conjugation of rhenium-188 to tumor targeting structures. The stereoisomeric tetrathiolato S4 ligands form very robust anionic five-coordinated oxorhenium(V) and oxotechnetium(V) complexes. Two routes for the preparation of the (188)Re(V) oxocomplexes with (iBu)2N(O)C-C(SH)C(SH)C(O)NH(CH2)3NH(CH2)3NHC(O)C(SH)C(SH)C(O)N(iBu)2 (ligand 1) and its hydrophilic crown ether derivative (ligand 2) were tested and optimized.