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.

journal_name

Bioorg Med Chem

authors

George GP,Stevens E,Åberg O,Nguyen QD,Pisaneschi F,Spivey AC,Aboagye EO

doi

10.1016/j.bmc.2013.12.012

subject

Has Abstract

pub_date

2014-01-15 00:00:00

pages

796-803

issue

2

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(13)01006-7

journal_volume

22

pub_type

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