Immunoscintigraphy of Venous Thrombi: Clinical Effectiveness of a New Antifibrin D-Dimer Monoclonal Antibody

Abstract

Safety and thrombus imaging capabilities of the 99mTc-labeled form of a new F(ab')2 monoclonal antibody (MoAb) against fragment D dimers from cross-linked human fibrin, previously shown to be effective labeled to 131I in detecting venous thrombi in the rabbit, were investigated. Sixteen patients (seven men, mean age: 60 ± 7 years) with deep (n = three) and superficial (n= 13) venous thromboses of the lower limbs documented at echo-Doppler study underwent, 24 hours before saphenous vein stripping, a scintigraphic study after IV injection of the 99mTc-MoAb (1,129 ± 275 MBq/mL), acquiring dynamic images, as well as early and delayed static images of lower limbs. Tracer activity was compared in normal and pathologic areas. At the operation, vessel wall including the thrombotic lesion was isolated, weighed, and counted. Blood radioactivity and MoAb concentra tion were also measured. No adverse reaction was observed after MoAb administration. Thrombus site appeared as a focal area (hot spot) of asymmetrically increased tracer uptake, already detectable at early images in all patients. All thrombi detected at echo-Doppler study (n=25) were confirmed at scintigraphic study, which showed four additional hot spots subsequently confirmed to represent thrombi at operation. Average percent ratio between pathologic and normal regions was 1.51 ± 1.34 (p < 0.05) at time-activity curves, 2.27 ± 1.1 (p < 0.05) at early static images, and 2.15 ± 1.2 (p < 0.05) at delayed images, respectively. Thrombus-to-blood uptake ratio was 4.3 ± 0.9 (p < 0.01). The F(ab')2 MoAb proved to be safe, and low levels of antimouse antibodies were detected in response, although further studies are needed to assess tolerance and effec tiveness in case of a second administration in the same patient. The 99mTc-labeled MoAb was very effective in identifying venous thromboses both at deep and superficial local izations, although its sensitivity and specificity need be evaluated in a more numerous group, including also patients with different and clinically more relevant localizations, such as caval thromboses. However, the possibility of obtaining high-quality images within 4 hours of MoAb administration is clinically relevant, and carries also therapeutic implications, especially in pulmonary thromboembolism.