{"id":{"repo_id":"kings","oai_identifier":"oai:kclpure.kcl.ac.uk:studenttheses/26b85a56-55d0-4128-8057-b6fef9993bf1"},"canonical_url":"https://search.dev.ndltd.org/etd/kings/oai:kclpure.kcl.ac.uk:studenttheses/26b85a56-55d0-4128-8057-b6fef9993bf1","repository":{"repo_id":"kings","name":"King's College London","base_url":"https://kclpure.kcl.ac.uk/ws/oai"},"display":{"title":"Evaluation of radiolabelled hynic-salmon calcitonin analogues as imaging agents for multiple myeloma and characterisation of novel hynic derivatives as chelators for technetium","abstract":"Calcitonin is a peptide hormone produced by the C-cells of the thyroids. Calcitonin receptors (CTR) are expressed by osteoclasts in the normal bone and in many cancers such as multiple myeloma (MM), breast and prostate cancer. In this thesis we report on the synthesis and evaluation of Tc-99m labelled salmon calcitonin (sCT) derivatives, sCTLys18-hynic-TFA and sCT(8-32)Lys18-hynic-TFA as potential imaging agents for MM and other CTR+ malignancies and the characterisation of novel hydrazinonicotinate (hynic) chelators. Following chemical characterisation in vitro stabilities of the radiopeptides were assessed on incubation in human serum. In vitro uptake studies in CTR+ MCF-7 cells confirmed that the Tc-99m labelled sCTLys18-hynic-TFA and sCT(8-32)Lys18-hynic-TFA were both ligands for CTR with nanomolar affinity. These findings also confirmed that the evolutionarily conserved disulfide loop in calcitonin peptides is not vital for receptor binding. We evaluated the radiopeptides in vivo in the 5T33 murine MM model. By using In-111-oxine labelled enhanced green fluorescence protein transfected 5T33 cells (eGFP-5T33) we confirmed that MM cells have a very high affinity to haemopoietic organs i.e. the liver, spleen and bone marrow. When imaging eGFP-5T33 myeloma bearing mice with Tc-99m labelled sCTLys18-hynic-TFA and sCT(8-32)Lys’8-hynic-TFA we found increased radiopeptide uptake in the liver, spleen and femora when compared to healthy controls. We could not establish correlation between radiopeptide uptake and the size of eGFP+ or CTR+ cell population in target organs. Our results suggest that the Tc-99m labelled hynic-sCT peptides may be capable of detecting changes caused by MM in the biology of the liver, spleen and bone marrow. Studies with novel hynic derivatives confirmed that hynic was most likely a bidentate chelator rather than a monodentate ligand in technetium complexes.","abstract_html":"Calcitonin is a peptide hormone produced by the C-cells of the thyroids. Calcitonin receptors (CTR) are expressed by osteoclasts in the normal bone and in many cancers such as multiple myeloma (MM), breast and prostate cancer. In this thesis we report on the synthesis and evaluation of Tc-99m labelled salmon calcitonin (sCT) derivatives, sCTLys18-hynic-TFA and sCT(8-32)Lys18-hynic-TFA as potential imaging agents for MM and other CTR+ malignancies and the characterisation of novel hydrazinonicotinate (hynic) chelators. Following chemical characterisation in vitro stabilities of the radiopeptides were assessed on incubation in human serum. In vitro uptake studies in CTR+ MCF-7 cells confirmed that the Tc-99m labelled sCTLys18-hynic-TFA and sCT(8-32)Lys18-hynic-TFA were both ligands for CTR with nanomolar affinity. These findings also confirmed that the evolutionarily conserved disulfide loop in calcitonin peptides is not vital for receptor binding. We evaluated the radiopeptides in vivo in the 5T33 murine MM model. By using In-111-oxine labelled enhanced green fluorescence protein transfected 5T33 cells (eGFP-5T33) we confirmed that MM cells have a very high affinity to haemopoietic organs i.e. the liver, spleen and bone marrow. When imaging eGFP-5T33 myeloma bearing mice with Tc-99m labelled sCTLys18-hynic-TFA and sCT(8-32)Lys’8-hynic-TFA we found increased radiopeptide uptake in the liver, spleen and femora when compared to healthy controls. We could not establish correlation between radiopeptide uptake and the size of eGFP+ or CTR+ cell population in target organs. Our results suggest that the Tc-99m labelled hynic-sCT peptides may be capable of detecting changes caused by MM in the biology of the liver, spleen and bone marrow. Studies with novel hynic derivatives confirmed that hynic was most likely a bidentate chelator rather than a monodentate ligand in technetium complexes.","abstract_has_math":false,"creators":["Meszaros, Levente"],"institution":"King's College London","degree_name":"Doctor of Philosophy","degree_level":"Doctoral Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Blower, Philip John","Calle, Yolanda"],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-1-1","date_published":"2013-1-1","updated_at":"2026-07-24T02:44:40Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:kclpure.kcl.ac.uk:studenttheses/26b85a56-55d0-4128-8057-b6fef9993bf1"],"render_values":[{"text":"oai:kclpure.kcl.ac.uk:studenttheses/26b85a56-55d0-4128-8057-b6fef9993bf1","href":null,"code":true}]}]},"links":{"outbound_url":"https://kclpure.kcl.ac.uk/portal/en/studentTheses/26b85a56-55d0-4128-8057-b6fef9993bf1","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Blower, Philip John","Calle, Yolanda"]},{"key":"dc:creator","label":"Author","values":["Meszaros, Levente"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013-1-1"]},{"key":"dc:date.issued","label":"Date","values":["2013-1-1"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Imaging Chemistry & Biology"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["King's College London"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://kclpure.kcl.ac.uk/portal/en/studentTheses/26b85a56-55d0-4128-8057-b6fef9993bf1"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:kclpure.kcl.ac.uk:studenttheses/26b85a56-55d0-4128-8057-b6fef9993bf1","https://kclpure.kcl.ac.uk/portal/en/studentTheses/26b85a56-55d0-4128-8057-b6fef9993bf1"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://kclpure.kcl.ac.uk/portal/files/13089703/Studentthesis-Levente_Meszaros_2013.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Calcitonin is a peptide hormone produced by the C-cells of the thyroids. Calcitonin receptors (CTR) are expressed by osteoclasts in the normal bone and in many cancers such as multiple myeloma (MM), breast and prostate cancer. In this thesis we report on the synthesis and evaluation of Tc-99m labelled salmon calcitonin (sCT) derivatives, sCTLys18-hynic-TFA and sCT(8-32)Lys18-hynic-TFA as potential imaging agents for MM and other CTR+ malignancies and the characterisation of novel hydrazinonicotinate (hynic) chelators. Following chemical characterisation in vitro stabilities of the radiopeptides were assessed on incubation in human serum. In vitro uptake studies in CTR+ MCF-7 cells confirmed that the Tc-99m labelled sCTLys18-hynic-TFA and sCT(8-32)Lys18-hynic-TFA were both ligands for CTR with nanomolar affinity. These findings also confirmed that the evolutionarily conserved disulfide loop in calcitonin peptides is not vital for receptor binding. We evaluated the radiopeptides in vivo in the 5T33 murine MM model. By using In-111-oxine labelled enhanced green fluorescence protein transfected 5T33 cells (eGFP-5T33) we confirmed that MM cells have a very high affinity to haemopoietic organs i.e. the liver, spleen and bone marrow. When imaging eGFP-5T33 myeloma bearing mice with Tc-99m labelled sCTLys18-hynic-TFA and sCT(8-32)Lys’8-hynic-TFA we found increased radiopeptide uptake in the liver, spleen and femora when compared to healthy controls. We could not establish correlation between radiopeptide uptake and the size of eGFP+ or CTR+ cell population in target organs. Our results suggest that the Tc-99m labelled hynic-sCT peptides may be capable of detecting changes caused by MM in the biology of the liver, spleen and bone marrow. Studies with novel hynic derivatives confirmed that hynic was most likely a bidentate chelator rather than a monodentate ligand in technetium complexes."]},{"key":"dc:title","label":"Title","values":["Evaluation of radiolabelled hynic-salmon calcitonin analogues as imaging agents for multiple myeloma and characterisation of novel hynic derivatives as chelators for technetium"]}]}],"canonical_facts":{"dc:contributor.advisor":["Blower, Philip John","Calle, Yolanda"],"dc:creator":["Meszaros, Levente"],"dc:date":["2013-1-1"],"dc:date.issued":["2013-1-1"],"dc:description.abstract":["Calcitonin is a peptide hormone produced by the C-cells of the thyroids. Calcitonin receptors (CTR) are expressed by osteoclasts in the normal bone and in many cancers such as multiple myeloma (MM), breast and prostate cancer. In this thesis we report on the synthesis and evaluation of Tc-99m labelled salmon calcitonin (sCT) derivatives, sCTLys18-hynic-TFA and sCT(8-32)Lys18-hynic-TFA as potential imaging agents for MM and other CTR+ malignancies and the characterisation of novel hydrazinonicotinate (hynic) chelators. Following chemical characterisation in vitro stabilities of the radiopeptides were assessed on incubation in human serum. In vitro uptake studies in CTR+ MCF-7 cells confirmed that the Tc-99m labelled sCTLys18-hynic-TFA and sCT(8-32)Lys18-hynic-TFA were both ligands for CTR with nanomolar affinity. These findings also confirmed that the evolutionarily conserved disulfide loop in calcitonin peptides is not vital for receptor binding. We evaluated the radiopeptides in vivo in the 5T33 murine MM model. By using In-111-oxine labelled enhanced green fluorescence protein transfected 5T33 cells (eGFP-5T33) we confirmed that MM cells have a very high affinity to haemopoietic organs i.e. the liver, spleen and bone marrow. When imaging eGFP-5T33 myeloma bearing mice with Tc-99m labelled sCTLys18-hynic-TFA and sCT(8-32)Lys’8-hynic-TFA we found increased radiopeptide uptake in the liver, spleen and femora when compared to healthy controls. We could not establish correlation between radiopeptide uptake and the size of eGFP+ or CTR+ cell population in target organs. Our results suggest that the Tc-99m labelled hynic-sCT peptides may be capable of detecting changes caused by MM in the biology of the liver, spleen and bone marrow. Studies with novel hynic derivatives confirmed that hynic was most likely a bidentate chelator rather than a monodentate ligand in technetium complexes."],"dc:identifier":["oai:kclpure.kcl.ac.uk:studenttheses/26b85a56-55d0-4128-8057-b6fef9993bf1","https://kclpure.kcl.ac.uk/portal/en/studentTheses/26b85a56-55d0-4128-8057-b6fef9993bf1"],"dc:identifier.uri":["https://kclpure.kcl.ac.uk/portal/files/13089703/Studentthesis-Levente_Meszaros_2013.pdf"],"dc:language":["eng"],"dc:publisher.department":["Imaging Chemistry & Biology"],"dc:publisher.institution":["King's College London"],"dc:relation.isreferencedby":["https://kclpure.kcl.ac.uk/portal/en/studentTheses/26b85a56-55d0-4128-8057-b6fef9993bf1"],"dc:title":["Evaluation of radiolabelled hynic-salmon calcitonin analogues as imaging agents for multiple myeloma and characterisation of novel hynic derivatives as chelators for technetium"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral Thesis"],"dc:type.qualificationname":["Doctor of Philosophy"]},"updated_at":"2026-07-24T02:44:40Z"}