Novel Peptide-Based PET Probe for Non-invasive Imaging of C‑X‑C Chemokine Receptor Type 4 (CXCR4) in Tumors

The
recently reported CXCR4 antagonist 3 (Ac-Arg-Ala-[DCys-Arg-2Nal-His-Pen]-CO2H) was investigated as a molecular scaffold for a CXCR4-targeted
positron emission tomography (PET) tracer. Toward this end, 3 was functionalized with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic
acid (DOTA) and 1,4,7-triazacyclononanetriacetic acid (NOTA). On the
basis of convincing affinity data, both tracers, [68Ga]­NOTA
analogue ([68Ga]-5) and [68Ga]­DOTA
analogue ([68Ga]-4), were evaluated for PET
imaging in “in vivo” models of CHO-hCXCR4
and Daudi lymphoma cells. PET imaging and biodistribution studies
revealed higher CXCR4-specific tumor uptake and high tumor/background
ratios for the [68Ga]­NOTA analogue ([68Ga]-5) than for the [68Ga]­DOTA analogue ([68Ga]-4) in both in vivo models. Moreover,
[68Ga]-4 and [68Ga]-5 displayed rapid clearance and very low levels of accumulation in
all nontarget tissues but the kidney. Although the high tumor/background
ratios observed in the mouse xenograft model could partially derive
from the hCXCR4 selectivity of [68Ga]-5, our
results encourage its translation into a clinical context as a novel
peptide-based tracer for imaging of CXCR4-overexpressing tumors.