Kenneth Millar

The in vivo release of 90Y from cyclic and acyclic ligand-antibody conjugates

Yttrium binding ligands DOTA, caDTPA and CT-DTPA were each conjugated to monoclonal antibody B72.3, labelled with 90Y and injected into mice in order to assess the in vivo inertness of the antibody-linked 90Y-ligand complexes. Levels of 90Y in femur shafts of the DOTA-B72.3 mice were low, being approximately 7 and 44%, respectively, of levels in the femur shafts of the caDTPA-B72.3 and CT-DTPA-B72.3 treated mice. This finding demonstrates the greater inertness and by implication the greater suitability for immunotherapy of the DOTA-90Y complex.

Synthesis of a kinetically stable yttrium-90 labelled macrocycle–antibody conjugate

Lysine is a precursor for the synthesis of an aminobutyl C-functionalised tetra-azacyclododecane tetra-acid which has been linked to B72.3 antibody and may be labelled with 90Y to form a kinetically stable complex of potential use in radioimmunotherapy.

Towards tumour imaging with indium-111 labelled macrocycle–antibody conjugates

C-Functionalised triazacyclododecane and triazacyclononane triacid macrocycles have been covalently attached to a monoclonal antibody and may be labelled with 111In to form kinetically inert radiolabelled complexes.

Potent and selective inhibitors of gelatinase-a 1. hydroxamic acid derivatives

Abstract A series of hydroxamic acid derivatives were prepared. By introducing aromatic substituents at the P1′ and P3′ positions highly potent gelatinase-A inhibitors, which possess a high degree of selectivity over collagenase and stromelysin, were obtained. These inhibitors may be of therapeutic value in the control of tumour metastasis.

Potent and selective inhibitors of gelatinase-A 2. carboxylic and phosphonic acid derivatives

Abstract A series of zinc binding groups was introduced into a pseudopeptide sequence containing aromatic groups in the P1′ position in order to obtain selective inhibitors of gelatinase-A. Carboxylic acid and phosphonic acid groups provided the most potent inhibitors

Synthesis of C- and N-functionalised derivatives of 1,4,7-triazacyclononane-1,4,7-triyltriacetic acid (NOTA), 1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetrayltetra-acetic acid (DOTA), and diethylenenetriaminepenta-acetic acid (DTPA): bifunctional complexing agents for the derivatisation of antibodies

Using (2S)-lysine as a precursor, the syntheses of aminobutyl derivatives of 1,4,7-triazacyclononane, 1,4,7,10-tetra-azacyclododecane, and 3-azapentane-1,5-diamine are described. Transformation into their reactive maleimide derivatives is described and alternative strategies for synthesising the title complexing agents involving nitrogen functionalisation are defined.

The synthesis of novel bifunctional linker molecules

Abstract We describe the synthesis of the novel bifunctional linker molecule 2-methyl, 2-(3-carboxypropyl)-cyclopent-4-en-1,3-dione and various related compounds. These compounds are highly thiol-specific.