Validating 123I-metaiodobenzylguanidine as a platelet marker for non-invasive imaging in rabbits.
BACKGROUND
Recent in vitro studies in our laboratory have demonstrated that platelets are necessary for leukocyte recruitment and airway remodelling in models of allergic airway inflammation, and also migrate to lung tissues in response to anti-IgE or relevant allergens in allergic asthma. Non-invasive imaging of platelet migration in vivo would provide a further insight into the roles of platelets in inflammatory diseases such as asthma, and metaiodobenzylguanidine (MIBG) was considered as a suitable platelet marker.


METHODS
The kinetics of MIBG uptake into rabbit platelets, the effect of MIBG on platelet function and the effect of platelet activation on MIBG uptake and retention were investigated. MIBG-labelled platelets were administered intravenously into rabbits and the time course of radioactivity in the lung and blood was monitored as a function of stimulation.


RESULTS
Following a 4h incubation of MIBG in rabbit PRP, a near maximal MIBG uptake (52.4 ± 20.2%) in platelets occurred. This time point was chosen for subsequent in vitro studies. In vitro platelet function studies showed that MIBG has no effect on ADP or PAF-induced platelet aggregation, PAF-induced thromboxane production or fMLP-induced platelet chemotaxis. However, serotonin showed a significant effect on MIBG uptake and retention, but only at high concentrations. Stimulation of rabbit platelets with ADP and PAF caused a significant release of stored MIBG in vitro. Following i.v. administration of MIBG labelled platelets, the response to i.v. ADP and PAF stimulation was small but significant.


CONCLUSIONS
The release of MIBG from platelets in vivo, particularly following stimulation, leads to high background levels. Therefore, MIBG may have limited utility as a label for imaging platelets in vivo using PET. However, it may be a useful marker in detecting pathological conditions where platelet migration is involved.
Saihkay
Hom N S
HN
The Sackler Institute of Pulmonary Pharmacology, Waterloo Campus, King's College London, London SE1 9NH, UK. hom.saihkay@kcl.ac.uk
Rickards
Karen J
KJ
Page
Clive P
CP
Ballinger
James R
JR
D019797:3-Iodobenzylguanidine / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D004912:Erythrocytes / Q000502:physiology; D007962:Leukocytes / Q000502:physiology; D008297:Male; D018384:Oxidative Stress; D010972:Platelet Activating Factor / Q000494:pharmacology; D015539:Platelet Activation; D010976:Platelet Count; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood / Q000378:metabolism*
D010972:Platelet Activating Factor; D019275:Radiopharmaceuticals; D012702:Serotonin Antagonists; D012701:Serotonin; D019797:3-Iodobenzylguanidine; D013929:Thromboxane B2; D000244:Adenosine Diphosphate