Rhenium and technetium-oxo complexes with thioamide derivatives of pyridylhydrazine bifunctional chelators conjugated to the tumour targeting peptides octreotate and cyclic-RGDfK

2017-08-21

North, Andrea J

Karas, John A

Ma, Michelle T

Blower, Philip J

Ackermann, Uwe

White, Jonathan M

Donnelly, Paul S

Journal Article

0000-0002-0707-6257

0000-0002-3349-7346

0000-0001-5373-0080

10.1021/acs.inorgchem.7b01247

This research aimed to develop new tumor targeted theranostic agents taking advantage of the similarities in coordination chemistry between technetium and rhenium. A γ-emitting radioactive isotope of technetium is commonly used in diagnostic imaging, and there are two β- emitting radioactive isotopes of rhenium that have the potential to be of use in radiotherapy. Variants of the 6-hydrazinonicotinamide (HYNIC) bifunctional ligands have been prepared by appending thioamide functional groups to 6-hydrazinonicotinamide to form pyridylthiosemicarbazide ligands (SHYNIC). The new bidentate ligands were conjugated to the tumor targeting peptides Tyr3-octreotate and cyclic-RGD. The new ligands and conjugates were used to prepare well-defined {M═O}3+ complexes (where M = 99mTc or natRe or 188Re) that feature two targeting peptides attached to the single metal ion. These new SHYNIC ligands are capable of forming well-defined rhenium and technetium complexes and offer the possibility of using the 99mTc imaging and 188/186Re therapeutic matched pairs.

link

Inorganic Chemistry 2017; 56(16): 9725-9741

Inorganic Chemistry