title: 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.
abstract: OBJECTIVE
  (99m)Tc-DI-DD3B6/22-80B3 (ThromboView, hereafter abbreviated to (99m)Tc-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 (99m)Tc-DI-80B3 Fab' in subjects with acute lower-limb DVT.
  
  
  METHODS
  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) (99m)Tc-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.
  
  
  RESULTS
  Thirty-five adverse events were reported in 15 of the 21 subjects. Those deemed possibly related to administration of (99m)Tc-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.
  
  
  CONCLUSIONS
  In subjects with acute DVT, (99m)Tc-DI-80B3 Fab' was well tolerated with favourable characteristics for the detection of acute venous thrombosis.
authors.affiliation: School of Medicine, University of Queensland, Brisbane, Australia. David_Macfarlane@health.qld.gov.au
authors.forename: David
authors.initials: D
authors.lastname: Macfarlane
authors.forename: Angelides
authors.initials: A
authors.lastname: Socrates
authors.forename: Paul
authors.initials: P
authors.lastname: Eisenberg
authors.forename: George
authors.initials: G
authors.lastname: Larcos
authors.forename: Paul
authors.initials: P
authors.lastname: Roach
authors.forename: Michael
authors.initials: M
authors.lastname: Gerometta
authors.forename: Richard
authors.initials: R
authors.lastname: Smart
authors.forename: Wendy
authors.initials: W
authors.lastname: Tsui
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scott
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005337:Fibrin / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D015609:Organotechnetium Compounds / Q000737:chemistry*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011874:Radiometry; D012449:Safety; D013194:Staining and Labeling; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D020246:Venous Thrombosis / Q000000981:diagnostic imaging* / Q000276:immunology
chemical_list: D007140:Immunoglobulin Fab Fragments; D015609:Organotechnetium Compounds; D005337:Fibrin
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