Selection of small pretargeting peptides with affinity for radiochelates and separation and purification of radiolanthanides
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The first objective of this dissertation was to develop metallated chelates with Michael acceptor groups for selecting small peptides from a random phage display library (RPL). The selection is for cysteine bearing peptides, so that the sulfhydryl on cysteine reacts with the reactive electrophilic group conjugated to the 1, 4, 7, 10- tetraazacyclododecane N, N', N'', N''', N'''' -tertraacetic acid (DOTA) chelate. Upon selection of peptides with affinity for the radiochelates, the antibody-conjugated peptides are used in pretargeting tumors. Three radionuclides (?�??�?Ga, ??????In, and ???�??�?Lu) were selected for labeling DOTA due to their nuclear properties applicable for radiopharmaceuticals, as well as their ability to form unique coordination geometries with the DOTA chelate. The latter variance is expected to contribute to selecting a peptide that binds specifically to each of the three metallated complexes. The newly synthesized chelate 2,2',2'',2'''-(2-(4-(4-amino-4-oxobut-2-enamido)benzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10- tetrayl)tetraacetic acid (AmMABD) was radiolabeled with ?�??�?Ga and ???�??�?Lu and the complexes were evaluated for their in vitro and in vivo stabilities and compared to previously reported radiolabeled complexes without electrophilic functional groups. The result from these studies showed the radiolabled (?�??�?Ga and ???�??�?Lu) AmMABD complexes were in vitro and in vivo stable. The encouraging biodistribution profile and fast blood clearance of the radiocongugates suggest that they are potential candidates for radiodiagnostic and radiotherapeutic agents. The second objective of this dissertation focuses on separation and purification of radiolanthanides to achieve high specific activity radioisotopes applicable in nuclear medicine. The reactor produced radiolanthanides, such as ???�??�?Lu, ???�???Tb and ???�??�?Ho, have nuclear properties useful for diagnos
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