In vivo examination of 111In-bis-5HT-DTPA to target myeloperoxidase in atherosclerotic ApoE knockout mice.
OBJECTIVE
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, (111)In-bis-5-hydroxytryptamide-diethylenetriamine-pentaacetate ((111)In-bis-5HT-DTPA).


METHODS
Bis-5HT-DTPA was synthesized. Oligomerization of bis-5HT-DTPA in the presence of MPO/H(2)O(2) 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 (111)In-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, (111)In-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.


CONCLUSIONS
This study described the pharmacokinetics and biodistribution of (111)In-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.
Department of Nuclear Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Ming-Che
MC
Wu
Hsin-I
HI
Ho
Te-Wei
TW
Lee
Hua-Lin
HL
Wu
Jem-Mau
JM
Lo
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000175:diagnosis* / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D009195:Peroxidase / Q000378:metabolism*; D011868:Radioisotopes / Q000493:pharmacokinetics; D012701:Serotonin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
C576377:111In-bis-5-hydroxytryptamide-diethylenetriamine-pentaacetate; D001057:Apolipoproteins E; D011868:Radioisotopes; D012701:Serotonin; D004369:Pentetic Acid; D009195:Peroxidase