title: Efficient [(18)F]AlF Radiolabeling of ZHER3:8698 Affibody Molecule for Imaging of HER3 Positive Tumors.
abstract: The human epidermal growth factor receptor 3 (HER3) is overexpressed in several cancers, being linked to a more resistant phenotype and hence leading to poor patient prognosis. Imaging HER3 is challenging owing to the modest receptor number (<50000 receptors/cell) in overexpressing cancer cells. Therefore, to image HER3 in vivo, high target affinity PET probes need to be developed. This work describes two different [(18)F]AlF radiolabeling strategies of the ZHER3:8698 affibody molecule specifically targeting HER3. The one-pot radiolabeling of ZHER3:8698 performed at 100 °C and using 1,4,7-triazanonane-1,4,7-triacetate (NOTA) as chelator resulted in radiolabeled products with variable purity attributed to radioconjugate thermolysis. An alternative approach based on the inverse electron demand Diels-Alder (IEDDA) reaction between a novel tetrazine functionalized 1,4,7-triazacyclononane-1,4-diacetate (NODA) chelator and the trans-cyclooctene (TCO) functionalized affibody molecule was also investigated. This method enabled the radiolabeling of the protein at room temperature. The [(18)F]AlF-NOTA-ZHER3:8698 and [(18)F]AlF-NODA-ZHER3:8698 conjugates showed a specific uptake at 1 h after injection in high HER3-expressing MCF-7 tumors of 4.36 ± 0.92% ID/g and 4.96 ± 0.65% ID/g, respectively. The current results are encouraging for further investigation of [(18)F]AlF-NOTA-ZHER3:8698 as a HER3 imaging agent.
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research , 123 Old Brompton Road, London SW7 3RP, U.K.
authors.forename: Chiara
authors.initials: C
authors.lastname: Da Pieve
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research , 123 Old Brompton Road, London SW7 3RP, U.K.
authors.forename: Louis
authors.initials: L
authors.lastname: Allott
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research , 123 Old Brompton Road, London SW7 3RP, U.K.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Martins
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research , 123 Old Brompton Road, London SW7 3RP, U.K.
authors.forename: Andrew
authors.initials: A
authors.lastname: Vardon
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research , 123 Old Brompton Road, London SW7 3RP, U.K.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Ciobota
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research , 123 Old Brompton Road, London SW7 3RP, U.K.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kramer-Marek
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research , 123 Old Brompton Road, London SW7 3RP, U.K.
authors.forename: Graham
authors.initials: G
authors.lastname: Smith
mesh_terms: D000535:Aluminum / Q000737:chemistry*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D005260:Female; D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D007553:Isotope Labeling; D061986:MCF-7 Cells; D051379:Mice; D008958:Models, Molecular; D049268:Positron-Emission Tomography / Q000379:methods*; D011487:Protein Conformation; D055550:Protein Stability; D020893:Receptor, ErbB-3 / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D000535:Aluminum; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3