PURPOSE: Pre-clinical experiments have demonstrated the accuracy of intravenous 99mTc labeled deimmunized anti-crosslinked fibrin (anti-D-dimer) Fab’ fragments (ThromboView®) for imaging thromboemboli with single photon emission computed tomography (SPECT). We now report the results of a phase 1b clinical study of ThromboView® combined with SPECT in patients with acute pulmonary thromboembolism.
METHODS: Patients (n = 14) were recruited based on contrast-enhanced helical CT scans demonstrating intra-luminal filling defects within segmental or larger pulmonary arteries, representing pulmonary thrombo-emboli. Within 72 hours of the CT scan acquisitions, ThromboView® (0.5 mg, 710-850 MBq 99mTc) was administered intravenously. Thoracic SPECT scans were acquired immediately, two hours and four hours after ThromboView® administration. The locations of SPECT scan “hot spots” (representing ThromboView® accumulations) were compared to the locations of pulmonary emboli detected by CT.
RESULTS: In all patients, pulmonary thrombo-emboli located independently within the proximal pulmonary arteries by CT scan corresponded to “hot spots” within the lung fields on the SPECT four hours after ThromboView® administration. Hot spots were identified consistently on axial, sagittal and coronal SPECT images. ThromboView® administration was well tolerated in all patients.
CONCLUSION: ThromboView® accumulations identified by SPECT (“hot spot” images), can disclose the locations of acute pulmonary thrombo-emboli in patients. ThromboView® directly highlights the emboli on the basis of their fibrin content, providing accurate diagnostic images. ThromboView® imaging can be performed in a clinically feasible time frame, is well-tolerated and avoids exposure to nephrotoxic radiographic contrast agents.
CLINICAL IMPLICATIONS: SPECT imaging with ThromboView® appears to be a useful diagnostic modality for detection of pulmonary thrombo-embolism, and this will be investigated in larger clinical studies. Detection based on crosslinked fibrin binding may be especially useful in situations where it is necessary to distinguish acute emboli (due to recent thrombosis) from other pathological entities within the pulmonary arteries, such as unresolved previous thrombo-emboli or intraluminal scars.
DISCLOSURE: Timothy Morris, Grant monies (from sources other than industry) ACCP CHEST Foundation: GlaxoSmithKline Distinguished Scholar in Thrombosis & NIH R21 HL080302-01: Chronic Thromboembolic Pulmonary Hypertension; Grant monies (from industry related sources) Agenix. Development of radiolabeled anti-D-dimer antibodies for clinical use in detecting acute pulmonary emboli; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. The potential of anti-D-Dimer antibodies for use as diagnostic agents to detect acute pulmonary thromboembolism.