Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 22, Issue 2, Pages 796-803Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2013.12.012
Keywords
PET; Gallium-68; Molecular imaging; TN14003; CXCR4
Funding
- Cancer Research UK-Engineering and Physical Sciences Research Council [C2536/A10337]
- UK Medical Research Council [MC_A652_5PY80]
- Medical Research Council and Department of Health (England)
- MRC [MC_U120081322] Funding Source: UKRI
- Cancer Research UK [10337] Funding Source: researchfish
- Medical Research Council [MC_U120081322] Funding Source: researchfish
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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 Ga-68, Cu-64 and In-111 as well as F-18 ((AlF)-F-18). 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 Ga-68-labelled tracer Ga-68-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 Ga-68, the comprehensive preclinical evaluation presented here suggests that Ga-68-CCIC16 is a promising PET tracer for the specific imaging of CXCR4-expressing tumours. (C) 2013 Elsevier Ltd. All rights reserved.
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