Innovative imaging for the assessment of cardiovascular risk modulation

This thesis explores innovative imaging techniques to detect and monitor inflammation and evaluates whether these can identify therapeutic modulation. Part I focuses on validating ⁶⁸Ga-DOTATATE PET/CT as a novel tool to image vascular inflammation, showing it can detect low-grade coronary inflammation in asymptomatic patients and is responsive to interventions like statins. Part I also discusses a first-in-human study of ^99mTc-fucoidan, targeting P-selectin.
Part II investigates therapeutic modulation of vascular inflammation. Semaglutide reduced bone marrow uptake but had no vascular effect, suggesting incomplete inflammatory suppression. A study using lanreotide, a somatostatin analogue, showed reduced vascular uptake of 68Ga-DOTATATE after treatment, likely due to competitive tracer binding, not true anti-inflammatory effects. Additionally, immune checkpoint inhibitors were associated with increased aortic inflammation in patients with Merkel cell carcinoma.
Part III shifts focus to dyslipidemia. A human study on trans-intestinal cholesterol excretion (TICE) using ursodeoxycholic acid (UDCA) failed to replicate LDL-lowering effects seen in mice. Finally, the future of PCSK9 targeting is explored, including gene editing via CRISPR, RNA-based therapies, and novel approaches like vaccines and adnectins.
Altogether, this thesis highlights the potential of molecular imaging to uncover inflammation not captured by systemic biomarkers, evaluate therapeutic interventions, monitor adverse treatment effects, and guide the development of innovative strategies targeting both inflammation and lipid metabolism to reduce cardiovascular risk.