Molecular imaging tracers targeting c-MET: a systematic review of preclinical evidence and clinical translation.

In 30 seconds

This PRISMA-guided systematic review assessed radioactive and fluorescent tracers targeting c-MET in preclinical and clinical studies. It included 50 preclinical and 13 clinical reports covering 62 distinct tracers; only four peptide-based tracers reached clinical evaluation. Clinical studies suggested that c-MET imaging is feasible, but diagnostic performance varied. Across studies, sample-size weighted average sensitivity and specificity were 81.7% and 39.3% for EMI-137, while cMBP-ICG, studied only in oral cavity cancer, had weighted averages of 85.5% and 91.1%. The authors identify limited and heterogeneous clinical evidence as a barrier to establishing clinical value.

Key findings

• Only four peptide-based tracers progressed to clinical evaluation: EMI-137, cMBP-ICG, ⁶⁸Ga-EMP-100, and ⁶⁸Ga-MetP.
• For EMI-137, weighted average sensitivity was 81.7% and specificity 39.3%; uptake in benign c-MET-expressing tissues limited diagnostic performance.
• In oral cavity cancer studies, cMBP-ICG had weighted average sensitivity of 85.5% and specificity of 91.1%, with tumour-to-background ratios of 2.7-4.1.
• All four clinically evaluated tracers had favourable reported safety, with only mild adverse events.

Why it matters

c-MET-targeted imaging may help visualise tumours and, in selected settings, identify malignant lesions or inform biopsy-site selection. However, benign-tissue uptake and variable diagnostic performance mean that tracer uptake cannot yet be assumed to distinguish malignancy reliably. The review highlights the need to interpret current findings in light of limited biological validation and heterogeneous study methods.

What to keep in mind

The review reports that clinical evidence is limited by methodological heterogeneity, small sample sizes, limited biological validation, and variable diagnostic performance.