Synthesis and Evaluation of Cyclic Peptide-Based PET Tracers Targeting ADAMTS4 for Early Detection and Monitoring of Aortic Aneurysms

Aortic aneurysm (AA), with high rupture risk and mortality,
lacks
accurate early diagnostic tools. Existing morphological imaging and
[18F]FDG PET show insufficient specificity, necessitating
AA-specific tracers. In this study, ADAMTS4, a regulator of vascular
wall cell proliferation and collagen repair, was verified as a potential
biomarker with high expression in human AA tissue. Based on an ADAMTS4-targeting
peptide, PET tracer precursor series (ADA1–ADA5) with varied
linkers were designed and synthesized, aiming to optimize pharmacokinetic
properties. Binding assays revealed that ADA2 showed the highest ADAMTS4
binding affinity among all, with ∼4-fold improvement compared
to unmodified peptide ADA0. Next, [68Ga]ADA1–[68Ga]ADA5 with satisfactory radiochemical properties were obtained
and subjected to PET/CT imaging. [68Ga]ADA2 exhibited optimal
AA uptake and the ability to localize ∼20% dilated aorta. Furthermore,
the tracer demonstrated favorable in vivo safety
and reduced renal uptake, highlighting its promise for the early detection
of AA progression and the identification of high-risk patients.