Reply: Results Confounded by a Disregard for Basic Dose–Response Radiobiology

REPLY: First, we would like to thank Dr. Kao for his elaborate comments regarding our article (1).

It is a matter of common sense that in cases of radioembolization, the determination of dose distribution is a challenging task because of the complexity of quantitative imaging and the limited availability of surrogate parameters for tissue (tumor) dosimetry.

Coming back to the blind men and the elephant, however, one should not mistake the pretherapeutic evaluation of intrahepatic ^99mTc-macroaggregated albumin (MAA) distribution with the posttherapeutic distribution of ⁹⁰Y microspheres. The work of Kao et al. (2) is a dosimetry study using the partition model and the ^99mTc-MAA accumulation pattern to predict the accumulated dose in target regions. In Kao’s study of hepatocellular carcinoma patients published in 2012, he assumes that “…^99mTc-MAA scintigraphy may be considered a ‘simulation study’ for ⁹⁰Y resin microsphere predictive dosimetry” (supplemental data of (2)), yet he acknowledges in his letter that “^99mTc-MAA is an imperfect surrogate for ⁹⁰Y microspheres.” The latter assumption is well in line with the evidence from several other studies that investigated ^99mTc-MAA and ⁹⁰Y microsphere distribution in different tumor entities (3–6). Consequently, relating ^99mTc-MAA distribution to the accumulated dose is a questionable practice.

In conclusion, we have the following major concerns about the comments made by Dr. Kao:

First, the study uses the partition model (2), which has been validated for dosimetry in only hepatocellular carcinoma patients (7). The basic assumption of the partition model is the equivalency between the accumulation pattern of the therapeutic agent (⁹⁰Y-labeled microspheres) and the accumulation pattern of the diagnostic surrogate (^99mTc-MAA). However, this equivalence has not been demonstrated for other tumor entities, especially not in colorectal carcinoma. Furthermore, several authors have reported discordant ^99mTc-MAA and ⁹⁰Y activity distributions (3–6).

Second, treatment planning should be based on a priori information to predict the intended response and total absorbed dose before therapeutic intervention as established in external-beam radiotherapy or brachytherapy. In contrast, using information from pre- and posttherapeutic examinations (^99mTc-MAA SPECT or Bremsstrahlung SPECT, for example) represents a validation process.

We agree that advanced imaging protocols using, for instance, cone-beam CT, Bremsstrahlung SPECT/CT or ⁹⁰Y PET/CT have an important role in the development of validation procedures for radioembolization. Nevertheless, these procedures do not compensate for the lack of an adequate diagnostic surrogate for pretherapeutic dosimetry.

In this regard, the conclusion of our study was that ⁹⁰Y-radioembolization-therapy “…should not be withheld from patients with colorectal liver metastases lacking intratumoral ^99mTc-MAA accumulation” (1).

Again, we thank Dr. Kao for his comments and discussion.

• © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.