Safety, pharmacokinetic and dosimetry evaluation of the proposed thrombus imaging agent 99mTc-DI-DD-3B6/22-80B3 Fab

• Published in: European journal of nuclear medicine and molecular imaging Vol. 33; no. 6; pp. 648 - 656
• Main Authors: Macfarlane, David J, Smart, Richard C, Tsui, Wendy W, Gerometta, Michael, Eisenberg, Paul R, Scott, Andrew M
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01.06.2006
• Subjects: Adolescent; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Body Burden; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Humans; Injections, Intravenous; Metabolic Clearance Rate; Middle Aged; Organ Specificity; Organotechnetium Compounds - administration & dosage; Organotechnetium Compounds - adverse effects; Organotechnetium Compounds - pharmacokinetics; Radiation Dosage; Radiation Injuries - diagnosis; Radiation Injuries - etiology; Radionuclide Imaging; Radiopharmaceuticals - administration & dosage; Radiopharmaceuticals - adverse effects; Radiopharmaceuticals - pharmacokinetics; Relative Biological Effectiveness; Risk Assessment; Risk Factors; Thrombosis - diagnostic imaging; Tissue Distribution; Whole-Body Counting
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-005-0025-y

(99m)Tc-DI-DD-3B6/22-80B3 (Thromboview, hereafter abbreviated to (99m)Tc-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 (99m)Tc-DI-80B3 Fab' in healthy volunteers. 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 (99m)Tc-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. 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. (99m)Tc-DI-80B3 Fab' had a rapid initial plasma clearance (t (1/2)alpha=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. (99m)Tc-DI-80B3 Fab' is well tolerated, is rapidly cleared and exhibits clinically acceptable dosimetry-characteristics well suited to a potential thrombus imaging agent.