Purpose: The aim of the study is to assess the feasibility of imaging specific activity of myeloperoxidase (MPO), a leukocyte-derived enzyme with important role in atherosclerosis, by SPECT/CT using a novel radiotracer, 111In-bis-5-hydroxytryptamide-diethylenetriamine-pentaacetate ( 111In-bis-5HT-DTPA). Methods: Bis-5HT-DTPA was synthesized. Oligomerization of bis-5HT-DTPA in the presence of MPO/H2O2 was studied and confirmed using MALDI-TOF. Apolipoprotein E knockout (ApoE KO) mice was used as an atherosclerosis-prone rodent model. Biodistribution assay and micro SPECT/CT imaging were carried out to prove the atherosclerosis targeting of 111In-bis-5HT-DTPA in the ApoE KO mice. Results: MALDI-TOF spectrum showed that the 5HT base agent can self oligomerize after activating by MPO. From the biodistribution study, 111In-bis-5HT-DTPA was quantified to be retained markedly higher while eliminated much slower in the aortas of the ApoE KO mice than that of the wild type (WT) mice within 1h post-injection. The nuclear imaging showed significantly higher uptake in the aorta of the ApoE KO mice than that of the WT mice at least within 2h post-injection. Conclusion: This study described the pharmacokinetics and biodistribution of 111In-bis-5HT-DTPA in ApoE KO mice and validated its utilization for early detection of atherosclerotic marker, MPO, in the aortic wall of atherosclerosis-prone rodent model.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science