A new class of oxotechnetium(5+) chelate complexes containing a TcON2S2 core

Molecular Design and Optimization of 99mTc-Labeled Recombinant Affibody Molecules Improves Their Biodistribution and Imaging Properties

“…The use of amino acids with hydrophilic (polar or charged) side chains in the N-terminal chelators provided reduced liver uptake and low levels of hepatobiliary excretion (14,(16)(17)(18)22), whereas the composition of the C-terminus was shown to be less influential in that aspect (23). However, in agreement with previously published data on chelator stability and biodistribution of 99m Tc-labeled proteins (24)(25)(26), the use of an N 3 S cysteine-based chelator at the C-terminus provided appreciably less release of 99m Tc-pertechnetate in the circulation than did the SN 3 chelator at the N-terminus (15,19,21). Furthermore, Ala 1 ,Glu 2 at the N-terminus has been shown to be associated with low hepatic uptake and low hepatobiliary excretion (19,(21)(22)(23).…”

“…Unfortunately, the exact mechanism for this phenomenon is unclear, and we pursued the minimization of renal uptake by designing a series of Affibody molecules with homologous chelators for the study of this structure-property relation. Cysteine-containing chelators placed at the C-terminus are intrinsically more stable than cysteine placed at the N-terminus because of a more favorable chelating geometry (26). We reasoned that by placing the chelator at the C-terminus, a minimal or no stabilizing effect from electron-donating side chains in the chelating sequence would be required for stability of the 99m Tc-complex in the circulation.…”

Targeting of HER2-Expressing Tumors with a Site-Specifically 99mTc-Labeled Recombinant Affibody Molecule, ZHER2:2395, with C-Terminally Engineered Cysteine

“…Placement of the cysteine residue in a C-terminal position allows for a more stable ''GGC''-type chelator, as previously demonstrated for scFv fragments and for technetium-labeled peptide radiopharmaceuticals (27). In a GGC-technetium complex, the N 3 S ligand set forms a stable chelate with three 5-member rings during complexation with the technetium; however, when the cysteine is located at the N-terminus (CGG), metal complexation through the cysteine yields a 6-member ring in the chelate, which is known to yield a less stable technetium(V) complex (28).…”

The preparation, characterization, and crystal and molecular structure of oxobis(ethan-1,2-dithiolato-S,µS′)technetium(V)oxo(ethan- 1,2-dithiolato-S,S′)technetium(V) [(TcO)2(SCH2CH2S)3]. A Tc(V) compound containing metal—sulfur—metal bridges

“…chemistry of Tc(V) has been dominated by the Tc0(3+) core and its affinity for sulfur-containing ligands (3). Sulfur can be used in combination with other ligating atoms and subsequently a series of TcON2S2 complexes was prepared (4), one of which undergoes rapid renal excretion ( 5 ) . The fast renal clearance fostered an interest in simplifying the synthesis of this important series of compounds because the thiol-protecting benzoyl groups employed rendered the amide thiolate ligands waterinsoluble, necessitating the use of biologically-compatible co-solvent, such as ethanol, in the preparation of the oxotechnetium complexes.…”