Positioning of 99mTc-chelators influences radiolabeling, stability and biodistribution of Affibody molecules.
Affibody molecules represent a novel class of affinity proteins with a high potential as tracers for radionuclide molecular imaging. In this comparative structure-property study, a series of Affibody molecules with the (99m)Tc-chelators maGGG, maSSS, or maESE attached to the epsilon-amine of the internally positioned K49 was prepared by peptide synthesis, for comparison to molecules with similar chelators positioned at the N-terminus. The conjugates were labeled with (99m)Tc and evaluated in vitro and in vivo. It was found that both composition and position of the chelating moiety influence the label stability, biodistribution and targeting properties of HER2-binding Affibody molecules.
School of Biotechnology, Royal Institute of Technology, AlbaNova University Centre, Stockholm, Sweden.
Torun
T
Ekblad
Anna
A
Orlova
Joachim
J
Feldwisch
Anders
A
Wennborg
Amelie Eriksson
AE
Karlström
Vladimir
V
Tolmachev
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry*; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry*; D014183:Transplantation, Heterologous
D002614:Chelating Agents; D015609:Organotechnetium Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; C544470:N(epsilon)49-mercaptoacetyl-glutamyl-seryl-glutamyl-ZHER2-342; C544468:N(epsilon)49-mercaptoacetyl-glycyl-glycyl-glycyl-ZHER2-342; C544469:N(epsilon)49-mercaptoacetyl-seryl-seryl-seryl-ZHER2-342; C533351:affibody (ZHER2-342)2