TO THE EDITOR:

Sarda et al. (1) have results that appear to confirm their previous acknowledgement that their preparation of ^99mTc-ciprofloxacin contained ^99mTc-colloid. However, they now state that their preparation of ^99mTc-ciprofloxacin “excluded a significant amount of radiolabeled colloids,” although details of the evidence for this statement are scant. We now know that some of the original 2-stage Infecton kits (^99mTc-ciprofloxacin) (unlike the new, 1-stage Infecton kit [Draximage]) tended to produce increasing amounts of colloid, particularly if they were diluted or if the pH or ionic strength of the preparation varied. This tendency may have depended, in part, on the ^99mTc generator used; the wet generators had a greater tendency than the dry type.

The clinical evidence for the presence of ^99mTc-colloid in the studies of Sarda et al. (1) is particularly obvious in their Figure 4, which appears to be a 4-h image. Changes typical of weight-bearing osteoarthritis are seen in the medial femoral and tibial condyles of the left knee. The active inflammation in the right knee would show persistent uptake of ^99mTc-colloid even when the ^99mTc-Infecton diffuses out. We conclude that their high sensitivity was due to the combination of ^99mTc-Infecton and ^99mTc-colloid and their poor specificity was due to diffusion of ^99mTc-Infecton from the osteoarthritic joints but persistence of ^99mTc-colloid.

Sarda et al. (1) stated that their results “were visually evaluated by 2 experienced nuclear medicine physicians unaware of the patient group… .” However, no data are presented that a learning curve was established for a new technique such as Infecton imaging. As is apparent from problematic results in some clinical publications (2), there is a learning curve for understanding the pharmacokinetics of Infecton and how they differ from the pharmacokinetics of radiolabeled white cells (3,4). Specific uptake of Infecton increases with time, until reaching a plateau at 24 h. Nonspecific uptake after the initial distribution decreases with time as the blood level falls. This is exemplified by the study of Larikka et al. (5), in which the specificity of Infecton for prosthetic hip infections was shown to increase greatly over time, having been 41% at 1 h, 68% at 4 h, and 95% at 24 h. Thus, obtaining 24-h images is essential for correct interpretation and should be standard practice for suspected bone and joint, cardiac valve, and vascular prosthesis infections. For all other suspected infections, 1- and 4-h images are usually sufficient.

It appears that Sarda et al. (1) have collected the region-of-interest data from anterior views only and from knees without knee supports. We know that a support for each knee is essential to achieve the same position in serial images of patients with pain or discomfort in their knees (6). The geometric mean of combined anterior and posterior regions expressed as a percentage of the injected activity when both knees are affected is the preferred method for reproducible quantitation, not a ratio between pairs of joints.

It is interesting that Sarda et al. (1) and Dumarey et al. (2)—the 2 groups of investigators who found reduced specificity in clinical studies—received Infecton kits from us for pilot studies but failed to communicate any problems with us. If they had done so, we could have checked the batch numbers of the kits they received to assess for any increased tendency to colloid formation. Other groups kept in touch with us about their problems and progress. We also know that, on occasion, quality control testing of the preparation may show negligible colloid soon after preparation but that under some circumstances colloid may form before injection if injection is delayed. The authors stated that only up to 1 h elapsed between preparation and injection, yet in a previous presentation of their data the injection was given up to 6 h after preparation. In contrast, the results of the groups who discussed their problems with us showed an overall mean sensitivity of 85% and mean specificity of 84% in a total of 1,405 patients, as summarized in our commentary on imaging bacterial infection (3). The multinational trial on 879 patients contained 194 patients with an orthopedic prosthesis, and a sensitivity of 96% and specificity of 91.6% were obtained (4).

The limitations of the 2-stage kit have been addressed by Draximage, the licensed manufacturer of Infecton kits. Its new 1-stage Infecton kit is beginning clinical trials. In conclusion, ^99mTc-Infecton is a bacteria-specific imaging agent if prepared correctly and used correctly and if the results are interpreted correctly.