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Erschienen in:
01.06.2006 | Original article
Safety, pharmacokinetic and dosimetry evaluation of the proposed thrombus imaging agent 99mTc-DI-DD-3B6/22-80B3 Fab′
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 6/2006
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Purpose
99mTc-DI-DD-3B6/22-80B3 (Thromboview, hereafter abbreviated to 99mTc-DI-80B3 Fab′) is a humanised, radiolabelled monoclonal antibody Fab′ fragment with high affinity and specificity for the D-dimer domain of cross-linked fibrin. The purpose of this study was to evaluate the safety, pharmacokinetics and dosimetry of four increasing doses of 99mTc-DI-80B3 Fab′ in healthy volunteers.
Methods
Thirty-two healthy volunteers (18–70 years; 16 male, 16 female) received a single intravenous injection of 0.5, 1.0, 2.0 or 4.0 mg of 99mTc-DI-80B3 Fab′. Safety outcomes (vital signs, electrocardiography, haematology, biochemistry, adverse events and development of human anti-human antibodies) were assessed up to 30 days post injection. Blood and urine samples were collected up to 48 h post injection. Gamma camera images were acquired at 0.5, 1, 2, 4, 6 and 24 h post injection. Dosimetry was performed using standard MIRD methodology.
Results
No adverse events considered to be drug related were observed. Human anti-human antibody was not detectable in any subject during the follow-up period. 99mTc-DI-80B3 Fab′ had a rapid initial plasma clearance (t
1/2α=1 h). The pharmacokinetic profile of the Fab′ fragment was generally linear across the four dose cohorts. By 24 h, 30–35% of the administered radioactivity appeared in the urine. There was marked renal accumulation with time, but no specific uptake was identified within other normal tissues. The effective dose was 9 mSv/750 MBq.
Conclusions
99mTc-DI-80B3 Fab’ is well tolerated, is rapidly cleared and exhibits clinically acceptable dosimetry—characteristics well suited to a potential thrombus imaging agent.