Improved synthesis and characterisation of a hydrazide derivative of diethylenetriaminepentaacetic acid for site-specific labelling of monoclonal antibodies with 111In

The monohydrazide derivative of diethylenetriaminepentaacetic acid, (HOOCCH2)2NCH2CH2N(CH2CO-OH)CH2CH2CH2N(CH2COOH)(CH2CO.NHNH2), is a bifunctional chelator designed for attaching the radiometal 111In selectively to the carbohydrate side chains of pre-oxidised monoclonal antibodies. A simple synthesis of this chelator (from diethylenetriaminepentaacetic acid cyclic anhydride and hydrazine), and its purification and chemical characterisation, are described. Rabbit IgG was oxidised with periodate, and the aldehyde groups thus generated were reacted with the linker forming a conjugate that was readily labelled in high yield and purity with 111In.