title: Improved tumor-to-organ ratios of a novel 67Ga-human epidermal growth factor radionuclide conjugate with preadministered antiepidermal growth factor receptor affibody molecules.
abstract: The overexpression of the epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis. Targeted nuclear imaging of the EGFR expression could improve the diagnostics in patients with HNSCC. However, the high expression of EGFR in normal organs may conceal the tumor uptake and therefore limit the use. This study assesses the biodistribution of a novel human epidermal growth factor (hEGF) radionuclide conjugate after preinjection with anti-EGFR affibody molecules. hEGF was conjugated with p-SCN-Bn-NOTA and labeled with (67)Ga. The biodistribution of [(67)Ga]Ga-NOTA-Bn-NCS-hEGF in nude mice with EGFR-expressing xenografts was evaluated either alone or 45 minutes after preinjection with one of the anti-EGFR affibody molecules Z(EGFR:1907), (Z(EGFR:1907))(2), or (Z(EGFR:955))(2). The novel radioimmunoconjugate, [(67)Ga]Ga-NOTA-Bn-NCS-hEGF, demonstrated high stability in vitro and specific binding to hEGF in vitro and in vivo. Preinjection with anti-EGFR affibody molecules improved the tumor-to-organ ratio in the liver, salivary glands, and colon. Overall, the dimeric high-affinity affibody molecule (Z(EGFR:1907))(2) exhibited the best results. These findings show that preblocking with an anti-EGFR affibody molecule is a promising tool that could improve the outcome of radionuclide-based imaging of EGFR-expressing tumors.
authors.affiliation: Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. karl.sandstrom@surgsci.uu.se
authors.forename: Karl
authors.initials: K
authors.lastname: Sandström
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Haylock
authors.forename: Irina
authors.initials: I
authors.lastname: Velikyan
authors.forename: Diana
authors.initials: D
authors.lastname: Spiegelberg
authors.forename: Heewa
authors.initials: H
authors.lastname: Kareem
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.forename: Hans
authors.initials: H
authors.lastname: Lundqvist
authors.forename: Marika
authors.initials: M
authors.lastname: Nestor
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005710:Gallium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D005710:Gallium Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; C051343:gadolinium 1,4,7-triazacyclononane-N,N',N''-triacetic acid; D066246:ErbB Receptors