Cox, Jonathan Paul Lawrence (1989) Yttrium macrocycles and their use in the treatment of cancer. Doctoral thesis, Durham University.
Six macrocyclic ligands have been synthesized for binding yttrium(III). Of the six, 1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid (DOTA) forms the most stable yttrium(III) complex in aqueous solution, log K(ML) = 24.9 and half life ~ 2 weeks at pH 1.0. In addition to an acid-dependent dissociative mechanism, release of Y(^3+) from Y(DOTA) may, it is tentatively suggested, be promoted by metal ions. DOTA also demonstrates rapid uptake of Y(^3+) (98% labelling efficiency at 310 K with [DOTA] = 10(^-5) M and [Y(^3+)1 ~ 10(^-9) M, pH 5.5 [0.1 M ammonium acetate]). Accordingly, an aminobutyl C-functionalised derivative of DOTA has been made and coupled to a monoclonal antibody. Once labelled with (^90)Y(^3+) a long range β- emitter, the conjugate can be used to selectively deliver a sterilising dose of radiation to a tumour. Preliminary experiments have indicated that the radiolabelled MoAb conjugate remains relatively inert in vivo. Tumour regression studies are in progress.
|Item Type:||Thesis (Doctoral)|
|Award:||Doctor of Philosophy|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||08 Feb 2013 13:39|