TO THE EDITOR:

We read with interest the recent article on the correlation of tumor radiation dose and response in patients with non-Hodgkin’s lymphoma by a dodecanetetraacetic acid–conjugated ⁹⁰Y-labeled humanized antibody to the cluster designation 22 antigen, epratuzumab. The authors stated that “tumor response did not correlate with the radiation dose delivered… ” (1).

We appreciate the authors’ citation, in their “Discussion” section, of our report (2) on tumor dosimetry for previously untreated patients who received ¹³¹I-tositumomab and on the correlation of estimated dose with response. In that section, they state: “Importantly, tumor dosimetry is biased because it can be performed only if the tumor is clearly seen, and in many instances there are tumor sites where either poor or even no targeting is achieved (1).” We agree with Sharkey et al. that if, in order to be evaluated for dosimetry, tumors must be seen on planar images, there clearly will be a bias toward the higher-uptake tumors. Such a bias can likely best be avoided if tumors are defined by methods other than scans obtained with the therapeutic agent. For example, using CT scans with registration to SPECT scans, as we have done, or using a dedicated SPECT/CT system, with the CT portion helping to define tumors, may avoid the potential bias that Sharkey et al. correctly point out as a pitfall.

Readers of our study (2) may have a misimpression concerning the measurements. The facts follow. Our method required a composite tumor to have an uptake visible on a set of tracer conjugate-view scans. The composite tumor was usually made up of more than one tumor (2). We called each tumor that composed the composite tumor an individual tumor. (By definition, the individual tumors were separated spatially on the patient’s CT scan (2).) Now, all of the individual tumors in the University of Michigan study of previously untreated patients were associated with a composite tumor that met the visible-uptake requirement. (This was not a difficult restriction because uptake was generally good.) However, it was not necessary for each of the individual tumors to have easily discernible uptake, because the volume of interest for which the uptake was measured on the SPECT scan was determined by the tumor region outlined on the CT scan. The tumor outline on the SPECT image was determined by registration of the SPECT scan to the CT scan, that is, effectively by a transfer of the CT-based volume of interest to the SPECT image set (2). Thus, a characteristic of our method was that dosimetry was estimated for all the individual tumors of which a composite tumor was composed, independent of the level of uptake within the individual tumors. This characteristic reduced the bias that Sharkey et al. discussed. We regret that we did not emphasize this degree of independence from bias in our article.

Regardless of our study, if a multiple-day series of SPECT images is acquired, starting immediately after radionuclide administration, and if a SPECT/CT system or SPECT-to-CT registration is used, then the radiation dose to each tumor identified on CT can be estimated, no matter what its radionuclide uptake. Thus, there clearly would not be a bias toward preferentially including tumors that exhibit high uptake.

In conclusion, we agree with Sharkey et al. that if, in order to be evaluated for dosimetry, tumors must be seen on planar images, there clearly will be a bias toward the higher-uptake tumors. In our study, we reduced bias by employing anatomic, CT, images and retrospective SPECT-to-CT registration. Definition of tumors on anatomic, CT or MRI, images with subsequent application to emission, SPECT or PET, images may well be the most potent approach to avoid bias in future dosimetric studies.