AbstractMolecular imaging is an attractive platform for noninvasive detection and assessment of cancer. In recent years, the targeted imaging of the C-X-C chemokine receptor 4 (CXCR4), a chemokine receptor that has been associated with tumor metastasis, has become an area of intensive research. This review article focuses on positron emission tomography (PET) and aims to provide useful and critical insights into the application of PET to characterize CXCR4 expression, including the chemical, radiosynthetic, and biological requirements for PET radiotracers. This discussion is informed by a summary of the different approaches taken so far and a comparison of their clinical translation. Finally, our expert opinions as to potential future advances in the field are expressed.
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.
This study reports the radiosynthesis of a new fluorine-18 glycosylated click cyanoquinoline [(18) F]5 for positron emission tomography imaging of epidermal growth factor receptor (EGFR). The tracer was obtained in 47.7?±?7.5% (n?=?3) decay-corrected radiochemical yield from 2-[(18) F]fluoro-2-deoxy-?-d-glucopyranosyl azide, and the overall nondecay-corrected radiochemical yield from aqueous fluoride was 8.6?±?2.3% (n?=?3). An in vitro preliminary cellular uptake study showed selectivity of the tracer for EGFR-positive A431 cell lines versus EGFR-negative MCF-7 cell lines. [(18) F]5 tracer uptake in A431 cells was significantly reduced by addition of the cold isotope analogue compound 5.
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