AI-designed dimeric 68Ga-PLEC PET tracer shows high uptake in PDAC xenografts

In a preclinical study, an AI-designed dimeric 68Ga-PLEC PET tracer achieved tumor uptake of 3.8 ± 0.5%ID/g at 30 min in pancreatic cancer xenografts, significantly higher than a monomeric tracer, with receptor-specific blockade.

• PLEC emerged as the top membrane-enriched, metastasis-linked candidate for PDAC via in silico screening.
• The dimeric tracer [68Ga]Ga-NOTA-FZPN-dimer showed higher affinity and cellular uptake than the monomer, with tumor uptake remaining higher at all imaging timepoints.
• Mechanistically, EP300-mediated acetylation at K1310 drives membrane relocalization of PLEC, providing biological support for PLEC-targeted imaging.

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