The design, synthesis, and evaluation of radiopharmaceuticals for actinium-225

Thesis type
(Thesis) M.Sc.
Date created
2021-11-08
Authors/Contributors
Abstract
This thesis studies the design, synthesis, and optimization of radiopharmaceuticals for targeted alpha therapy applications with actinium-225 (225Ac). In Chapter 2, three novel radiopharmaceuticals - 2.1 (DOTA-CCZ-N-Me-α-CycMSH), 2.2 (Macropa-CCZ-N-Me- α-CycMSH), and 2.6 (Macropa-α-CycMSH) for malignant melanoma therapy were labeled with 225Ac and evaluated. All three radiopharmaceuticals exhibited excellent in vitro stability, while Macropa-CCZ-N-Me-α-CycMSH showed lower tumor uptake and moderate normal tissue uptake. In Chapter 3, a total of 5 diaza-18-crown-6 macrocyclic ligands (macropa, macropaquin, macroquin-SO3, macrohopo, and macrohopo') as chelators for 225Ac were investigated. Two of the chelators (macrohopo and macrohopo') which contain hydroxypyridinone pendant donor arms are novel and were synthesized/characterized in this work. Macropaquin was able to quantitively radiolabel at chelator concentrations as low as 10-6 M at ambient temperatures within one hour, while chelator macrohopo was unable to achieve 225Ac complexation under any conditions. This thesis showcases the complexity of radiopharmeticuals, in particular for 225Ac.
Document
Identifier
etd21704
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Copyright is held by the author(s).
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This thesis may be printed or downloaded for non-commercial research and scholarly purposes.
Supervisor or Senior Supervisor
Thesis advisor: Ramogida, Caterina
Language
English
Member of collection
Attachment Size
input_data\21666\etd21704.pdf 9.72 MB