Targeted molecular imaging is a valuable method in cancer diagnosis.The palette of manganese isotopes provides an excellent opportunity for bimodal imaging,given that it possesses a long-lived positron-emitting isotop...Targeted molecular imaging is a valuable method in cancer diagnosis.The palette of manganese isotopes provides an excellent opportunity for bimodal imaging,given that it possesses a long-lived positron-emitting isotope usable in functional Positron Emission Tomography(PET)imaging(^(52)Mn),while the paramagnetic nature of 55Mn makes monoaquated complexes of Mn(Ⅱ)suitable for Magnetic Resonance Imaging(MRI).Present study reports on the synthesis of series of new model bifunctional Mn(Ⅱ)chelators(BFC)derived from the rigid 3,9-PC2A ligand and on the studies of physicochemical properties of their Mn(Ⅱ)chelates.From these,the 3,9-PC2ABn^(pCO2H)platform was selected for bioconjugation and for further in vivo studies.Anti-HER2 affibody was used as a highly specific binding protein,which was expressed in a prokaryotic system,purified by affinity chromatography followed by RP-HPLC.The specificity of the affibody for HER2 receptors was proved following its conjugation with AlexaFluor555 dye.Finally the affibody was conjugated with the selected 3,9-PC2ABn^(pCO2H)BFC and[^(52)Mn]Mn(Ⅱ)labelling was performed.The labelled conjugate was tested in a pilot study by PET imaging using MDA-MB(HER2+)and 4T1(HER2−)tumour-bearing mice.The results demonstrate that the[[^(52)Mn]Mn(3,9-PC2ABn^(pMA))(H_(2)O)]-Cys-HER2-affibody conjugate is an efficient and specific molecular vehicle for targeting and visualizing HER2+tumours by^(52)Mn-based PET imaging.展开更多
基金supported by the Doctoral School of Chemistry at the University of Debrecen,Debrecen,Hungarysupported by the Gedeon Richter’s Talentum Foundation established by Gedeon Richter Plc(Gedeon Richter Ph.D.Fellowship)+6 种基金The research was prepared with professional support from the Doctoral Student Scholarship Program of the Cooperative Doctoral Program of the Ministry of Innovation and Technology financed by the National Research,Development,and Innovation Fund(NKFIH)The authors thank the financial support from the Hungarian National Research,Development,and Innovation Office(NKFIH K-128201 and K-134694 projects)supported by the project TKP2021-NKTA-42 financed by the National Research,Development and Innovation Fund of the Ministry for Innovation and Technology,HungaryThis work was supported by the following grants from the Romanian Ministry of Education and Research,CCDI-UEFISCDI,project number:PN-iII-P2-2.1-PED-2019-4184,within PNCDI III,acronym NARADPN-iII-P1-1.2-PCCDI-2017-0737,within PNCDI III,acronym ARTEMISPN-iII-P1-1.2-PCCDI-2017-0769,within PNCDI III,acronym ONCORADthe Romanian Academy and the Hungarian Academy of Sciences through the bilateral collaboration agreement no.3698 of 13.09.2018“Mobility projects”for scientific projects carried out in collaboration。
文摘Targeted molecular imaging is a valuable method in cancer diagnosis.The palette of manganese isotopes provides an excellent opportunity for bimodal imaging,given that it possesses a long-lived positron-emitting isotope usable in functional Positron Emission Tomography(PET)imaging(^(52)Mn),while the paramagnetic nature of 55Mn makes monoaquated complexes of Mn(Ⅱ)suitable for Magnetic Resonance Imaging(MRI).Present study reports on the synthesis of series of new model bifunctional Mn(Ⅱ)chelators(BFC)derived from the rigid 3,9-PC2A ligand and on the studies of physicochemical properties of their Mn(Ⅱ)chelates.From these,the 3,9-PC2ABn^(pCO2H)platform was selected for bioconjugation and for further in vivo studies.Anti-HER2 affibody was used as a highly specific binding protein,which was expressed in a prokaryotic system,purified by affinity chromatography followed by RP-HPLC.The specificity of the affibody for HER2 receptors was proved following its conjugation with AlexaFluor555 dye.Finally the affibody was conjugated with the selected 3,9-PC2ABn^(pCO2H)BFC and[^(52)Mn]Mn(Ⅱ)labelling was performed.The labelled conjugate was tested in a pilot study by PET imaging using MDA-MB(HER2+)and 4T1(HER2−)tumour-bearing mice.The results demonstrate that the[[^(52)Mn]Mn(3,9-PC2ABn^(pMA))(H_(2)O)]-Cys-HER2-affibody conjugate is an efficient and specific molecular vehicle for targeting and visualizing HER2+tumours by^(52)Mn-based PET imaging.
