published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

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The gadolinium ((^153)Gd) complexes of 21 aza-phosphinic and aza-carboxylic acid macrocycles based on 1,4,7,10- tetraazacyclododecane were studied as possible contrast agents for magnetic resonance imaging. The acid dissociation rates and partition coefficients of gadolinium complexes were measured and related to their in vivo stability and route of elimination in mice. The anionic aza-phosphinic acids had low acid dissociation rates (24-78 x l0(^6) sec (^-1) at pH 1) which correlated with high in vivo stability (<0.025% dose in the skeleton at 24 hours). [Gd.l2N4P4Bz4]" shows potential as a gall bladder, bile duct contrast imaging agent at doses of 0.1 to 10 µmol/kg , and for tumour detection within the hepatobiliary system at doses of 100 to 200 µmol /kg .Macrocycles based on l,4,7,10-tetraazacyclododecane can be used to complex yttrium (90y) for tumour therapy. 90y complexes of aza-phosphinic and aza-carboxylic acid derivatives showed slow acid catalysed dissociation rates of 1-14 X 10"6 sec'l at pH 1, and rapid association kinetics of greater than 80% yttrium uptake within 30 minutes at 5 µM ligand. A tetraaza-carboxylic acid and a tri-phosphinic acid derivative modified with maleimide were linked to monoclonal antibodies and labelled with 90y. Both were highly stable in vivo with <0.0l% 90y dose in the mouse femur shaft at 48 hours.Seven aza-phosphinic and aza-carboxylic acid macrocycles based on i,4,7,-triazacyclononane were labelled with radioactive gallium or indium. Gallium complexes were generally more stable in vivo than the corresponding indium complexes. Three 67Ga and two min complexes showed potential as imaging agents and one gallium complex as a hepatobiliary imaging agent. Several complexes were examined as possible tumour localisation agents, [Ga.9N3] giving a tumour to blood ratio of 22:1 at 4 hours after injection.

Thesis (M.D.)--University of Adelaide, Dept. of Surgery, 1984. / Some mounted ill. Includes bibliographical references (leaves 147-194).

Thesis (Ph.D.)--University of Texas at Dallas, 2008. / Includes vita. Includes bibliographical references (leaves 150-158)

Thesis (Ph.D.)--University of Texas at Dallas, 2005. / Includes vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 89-116). Also available in print.

Thesis (Ph.D.)--University of Hong Kong, 2001. / Includes bibliographical references. Also available in print.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 4 uppsatser.

Thesis (Ph. D.)--RAND Graduate School, 1998. / "RGSD-146"--Cover p. 4. Includes bibliographical references (p. 105-111).