title: Preclinical evaluation of a CXCR4-specific (68)Ga-labelled TN14003 derivative for cancer PET imaging.
abstract: Molecular imaging is an ideal platform for non-invasive detection and assessment of cancer. In recent years, the targeted imaging of CXCR4, a chemokine receptor that has been associated with tumour metastasis, has become an area of intensive research. In our pursuit of a CXCR4-specific radiotracer, we designed and synthesised a novel derivative of the CXCR4 peptidic antagonist TN14003, CCIC16, which is amenable to radiolabelling by chelation with a range of PET and SPECT radiometals, such as (68)Ga, (64)Cu and (111)In as well as (18)F (Al(18)F). Potent in vitro binding affinity and inhibition of signalling-dependent cell migration by unlabelled CCIC16 were confirmed by a threefold uptake in CXCR4-over-expressing cells compared to their isogenic counterparts. Furthermore, in vivo experiments demonstrated the favourable pharmacokinetic properties of the (68)Ga-labelled tracer (68)Ga-CCIC16, along with its CXCR4-specific accumulation in tissues with desirable contrast (tumour-to-muscle ratio: 9.5). The specificity of our tracer was confirmed by blocking experiments. Taking into account the attractive intrinsic PET imaging properties of (68)Ga, the comprehensive preclinical evaluation presented here suggests that (68)Ga-CCIC16 is a promising PET tracer for the specific imaging of CXCR4-expressing tumours.
authors.affiliation: Comprehensive Cancer Imaging Centre, Imperial College London, Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom; Department of Chemistry, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom. Electronic address: g.george09@imperial.ac.uk.
authors.forename: Guillaume P C
authors.initials: GP
authors.lastname: George
authors.affiliation: Comprehensive Cancer Imaging Centre, Imperial College London, Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stevens
authors.affiliation: Comprehensive Cancer Imaging Centre, Imperial College London, Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: Ola
authors.initials: O
authors.lastname: Åberg
authors.affiliation: Comprehensive Cancer Imaging Centre, Imperial College London, Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: Quang-Dé
authors.initials: QD
authors.lastname: Nguyen
authors.affiliation: Comprehensive Cancer Imaging Centre, Imperial College London, Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: Federica
authors.initials: F
authors.lastname: Pisaneschi
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Spivey
authors.affiliation: Comprehensive Cancer Imaging Centre, Imperial College London, Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005710:Gallium Radioisotopes; D006801:Humans; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000175:diagnosis*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D049268:Positron-Emission Tomography; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D005710:Gallium Radioisotopes; D010455:Peptides; D019718:Receptors, CXCR4; C488289:TN14003
keywords: CXCR4; Gallium-68; Molecular imaging; PET; TN14003