Original ArticlePulmonary Emboli Imaging with 99mTc-labelled Anti-D-dimer (DI-80B3) Fab′ Followed by SPECT
Section snippets
Background
Mortality from acute pulmonary embolism (PE) remains a substantial public health care problem [1]. Autopsy series suggest that death from acute PE is at least three-fold higher than the current clinical incidence estimates of PE [2], [3], [4], [5], [6], which suggests that limitations in current diagnostic approaches may leave a proportion of patients with PE undiagnosed and therefore untreated. Improvements in the ability to diagnose PE would be especially beneficial in light of the excellent
Study Population
Adults diagnosed with acute PE at the participating medical centres were considered for enrolment in the study. Inclusion criteria were: (1) ability to give informed consent; (2) onset of PE-related symptoms in the seven days prior to enrolment; (3) presence of PE, defined as intra-luminal filling defects in segmental or larger pulmonary arteries on multi-detector CTPA; (4) ability to receive injection of 99mTc-DI-80B3 Fab′ within 72 hours of the CTPA; (5) men or non-pregnant women, aged 18
Characteristics of the Subjects
Sixteen subjects with acute pulmonary emboli were enrolled in the study. One subject did not receive 99mTc-DI-80B3 due to equipment failure on the study day. The remaining 15 received 99mTc-DI-80B3. One subject withdrew consent prior to imaging and pharmacokinetic analysis, but agreed to continue with safety assessments. The remaining 14 subjects underwent imaging and pharmacokinetic analysis. All 14 subjects had evaluable 99mTc-DI-80B3 imaging and pharmacokinetic data. One of these subjects
Discussion
The results of this study indicate that intravenous 99mTc-DI-80B3 administration is safe in patients with acute PE. It was associated with no serious adverse effects and no detectable antibody responses. This is consistent with the results of similar studies in normal volunteers [12] and patients with deep venous thrombosis [15]. Transient and asymptomatic elevations in liver enzymes were observed in three patients in the first week after 99mTc-DI-80B3 administration, although those patients
Conclusion
The technique of SPECT scanning after administration of 99mTc-DI-80B3 appeared to be safe in patients with acute PE, and shows promise as an alternative method of PE diagnosis. The imaging data from this study are being used to optimise the image acquisition and interpretation for subsequent Phase II studies.
Competing Interests
This study was funded by a research grant from AGEN Biomedical Ltd. Drs. Gerometta and Ms. Tsui were employees of AGEN Biomedical Ltd., Dr. Eisenberg was a consultant to AGEN Biomedical Ltd. and held 50,000 shares of Agen stock (currently no value) and Dr. Macfarlane was a consultant to AGEN Biomedical Ltd. during the performance of the study. Dr. Morris received research support for this study and other studies concerning the same agent from AGEN Biomedical Ltd. and his travel to the
Authors’ Contributions
TM, MG, PE, RS and DM conceived of and designed the study. DM was the principal coordinating investigator for the enrolment sites. RS, WT and DM reviewed the raw acquisition data. PR, NB, KT and SU contributed to the study design, acted as site principal investigators and assisted in the analysis of the final results. All authors read, edited and approved of the final manuscript.
Authors’ Information
Not applicable.
Acknowledgements
The authors would like to acknowledge the expert image interpretations provided by Dr. Richard Slaughter who reviewed the CT images; Drs. Paul Thomas, Fred Khafagi, and John Hunter who initially reviewed the 99mTc-DI-80B3 to optimise the imaging parameters and develop the image interpretation guide; as well as Drs. Scott Beuzeville and. Ernest Belezzuoli who reviewed the 99mTc-DI-80B3 SPECT scans diagnostically. They thank Peter Chiles for assistance with the illustrations for the manuscript
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