Abstract
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 1 h 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 2 h 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.
Acknowledgments
The authors would like to thank Dr. Shin-Lin Shih, Department of Radiology, Mackay Memorial Hospital, and Dr. Hung-I Yeh, Department of Cardiology, Mackay Memorial Hospital, for their kind advices on the research focus of MPO detection and the use of ApoE KO mice as a more practical animal model for this study. Technical assistances to this work of Wan-Jou Chen, Su-Tang Lo and Chun-Hui Tsai are very much appreciated.
Declaration of interest
This study is supported by a research grant from Mackay Memorial Hospital and financial aid from the National Tsing Hua University.