Reply:

We thank Drs. Weinmann and Moretti for their comments and note their concern over the inclusion in our study (1) of patients with discordant results on the 3 sets of ^99mTc-apcitide images, which suggested that the final overall sensitivity of the test was “falsely” high.

As stated in our article (1), the major purpose of our study was to compare the diagnostic accuracy of early and delayed ^99mTc-apcitide scintigraphy in patients with suspected acute deep vein thrombosis (ADVT) of the lower extremities. The major conclusion of the study was that although images obtained at 2 h after ^99mTc-apcitide injection show the greatest overall accuracy compared with earlier images, combined analysis of image sets from at least 2 time points provides greater accuracy in the detection of ADVT. Therefore, it was clear that it was necessary to use both static and temporal criteria to obtain a high diagnostic accuracy. Although the 3 sets of images were all positive for a given patient in 54.5% (12/22) of patients with proven ADVT, ^99mTc-apcitide studies with false-negative findings in 1 or more sets of images were seen in 10 cases. ^99mTc-apcitide scintigraphy was positive in at least 2 sets of images in 3 cases, positive only on the delayed images in another 3 cases, and totally negative in 3 patients. ^99mTc-apcitide scintigraphy was positive at 10 min in 1 patient only (and not in 2 patients as stated in the above Letter to the Editor). In this particular case, in a subanalysis looking at the diagnostic certainty of the test (not published yet), the ^99mTc-apcitide study was read as definitely abnormal at 10 min and probably normal at 60 and 120 min, although the asymmetry of the vascular uptake was persistent but judged to be not significant on the separate reading by the observers who were blinded to the experiment. After the 3 images had been analyzed together, the observers agreed that this case should be read as positive for ADVT, taking into consideration the aspect of the asymmetrical vascular uptake on the 3 sets of images. Access to the 3 sets of images together was definitely beneficial to the observers, especially in more difficult cases.

Although ^99mTc-apcitide uptake has been described at various degrees in cellulitis or hematoma, these conditions usually can be differentiated from ADVT by the extent, shape, and localization of the uptake. Other possible explanations will have to be evaluated to understand why some cases show more initial uptake, such as the size, localization, and age of the thrombus; the effect of anticoagulant and antiplatelet medication; and other localized hemodynamic parameters.

We must remind readers that ^99mTc-apcitide scintigraphy is a novel type of diagnostic imaging procedure now available in clinical nuclear medicine. Therefore, criteria for positive and negative tests must be established and tested against a gold-standard method for ADVT, even an imperfect one such as contrast-enhanced venography. It is likely that the accuracy of ^99mTc-apcitide scintigraphy will improve with more extensive clinical experience. However, preliminary results of investigative studies performed with other radiolabeled peptides in the detection of ADVT (2) seem to confirm that changes of uptake or target-to-background ratio over time are important criteria in the diagnosis of ADVT, as demonstrated in our study.