Imaging of deep venous thrombosis in patients using a radiolabelled anti-D-dimer Fab′ fragment (99mTc-DI-DD3B6/22-80B3): results of a phase I trial
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99mTc-DI-DD3B6/22-80B3 (ThromboView®, hereafter abbreviated to 99mTc-DI-80B3 Fab′) is a radiolabelled humanised monoclonal Fab′ fragment with affinity and specificity for D-dimer domains of cross-linked fibrin. Detection of thromboembolic events has been demonstrated in canine models. The study objectives were evaluation of safety and characterisation of biodistribution, immunogenicity and pharmacokinetic profile of increasing doses of 99mTc-DI-80B3 Fab′ in subjects with acute lower-limb DVT.
Twenty-six patients with acute lower limb DVT were enrolled. Of these, 21 received a single intravenous dose of 0.5 mg (n = 6), 1.0 mg (n = 9) or 2 mg (n = 6) 99mTc-DI-80B3 Fab′. Blood and urine samples and gamma camera images were collected to 24 h after administration for pharmacokinetic and dosimetry analysis. Vital signs, electrocardiography, hematological and biochemical data and human anti-human antibody (HAHA) levels were monitored for up to 30 days following administration. Patients were assigned to either planar or single photon emission computed tomographic (SPECT) imaging of the thorax at 4 h following injection.
Thirty-five adverse events were reported in 15 of the 21 subjects. Those deemed possibly related to administration of 99mTc-DI-80B3 Fab′ included mild hypertension, mild elevation of LD (lactate dehydrogenase) and moderate elevation of ALT (alanine transaminase). HAHA assays remained negative. Pharmacokinetics and organ dosimetry were comparable to prior normal volunteer data. Localisation of Thromboview® to sites of known thrombus was evident as early as 30 min post-injection.
In subjects with acute DVT, 99mTc-DI-80B3 Fab′ was well tolerated with favourable characteristics for the detection of acute venous thrombosis.
KeywordsTechnetium chemistry Technetium radiopharmaceuticals Radiolabelled proteins–peptides Pulmonary embolism Molecular imaging
The authors acknowledge the assistance of Prof. SP Butler of St. George Hospital, Sydney, Australia in the recruitment of patients.
Conflict of interest
AGEN Biomedical Limited sponsored and financially supported this trial. Dr. Macfarlane and Prof. Scott were the principal investigators during the study. Dr. Macfarlane currently acts as a consultant to AGEN Biomedical Limited for product and protocol development. Professor Eisenberg is also a consultant to AGEN Biomedical Limited and Dr. Gerometta is an employee of AGEN Biomedical Limited. Wendy Tsui is employed by the University of New South Wales under a research contract between AGEN Biomedical Limited and the university. Professor Scott currently serves as a consultant to Agen Biomedical Limited.
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