Design, synthesis and biological evaluation of a multifunctional HER2-specific Affibody molecule for molecular imaging
Tran, TA; Rosik, D; Abrahmsén, L; Sandström, M; Sjöberg, A; Wållberg, H; Ahlgren, S; Orlova, A; Tolmachev, V
| HERO ID | 4759430 |
|---|---|
| In Press | No |
| Year | 2009 |
| Title | Design, synthesis and biological evaluation of a multifunctional HER2-specific Affibody molecule for molecular imaging |
| Authors | Tran, TA; Rosik, D; Abrahmsén, L; Sandström, M; Sjöberg, A; Wållberg, H; Ahlgren, S; Orlova, A; Tolmachev, V |
| Journal | European Journal of Nuclear Medicine and Molecular Imaging |
| Volume | 36 |
| Issue | 11 |
| Page Numbers | 1864-1873 |
| Abstract | <strong>PURPOSE: </strong>The purpose of this study was to design and evaluate a novel platform for labelling of Affibody molecules, enabling both recombinant and synthetic production and site-specific labelling with (99m)Tc or trivalent radiometals.<br /><br /><strong>METHODS: </strong>The HER2-specific Affibody molecule PEP05352 was made by peptide synthesis. The chelator sequence SECG (serine-glutamic acid-cysteine-glycine) was anchored on the C-terminal to allow (99m)Tc labelling. The cysteine can alternatively serve as a conjugation site of the chelator DOTA for indium labelling. The resulting (99m)Tc- and (111)In-labelled Affibody molecules were evaluated both in vitro and in vivo.<br /><br /><strong>RESULTS: </strong>Both conjugates retained their capacity to bind to HER2 receptors in vitro and in vivo. The tumour to blood ratio in LS174T xenografts was 30 at 4 h post-injection for both conjugates. Biodistribution data showed that the (99m)Tc-labelled Affibody molecule had a fourfold lower kidney accumulation compared with the (111)In-labelled Affibody molecule while the accumulation in other organs was similar. Gamma camera imaging of the conjugates could clearly visualise the tumours 4 h after injection.<br /><br /><strong>CONCLUSION: </strong>Incorporation of the C-terminal SECG sequence in Affibody molecules provides a general multifunctional platform for site-specific labelling with different nuclides (technetium, indium, gallium, cobalt or yttrium) and for a flexible production (chemical synthesis or recombinant). |
| Doi | 10.1007/s00259-009-1176-z |
| Pmid | 19504093 |
| Wosid | WOS:000270980400017 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |