Page 38 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 2
coincidences that do not intersect the rod source (within a certain distance) and, as such, it reduces the influence of scatter, randoms, and emission spillover. To further validate quantitative accuracy, a comparison was made between blood pool activity seen in the PET scanner versus those in manual samples.
Quantification of blood pool activity in the left ventricle of the heart showed good agreement with the sampled blood activity, except for a few heavy weight patients (> 100 kg). This suggests that immuno-PET with 89Zr-cmAb U36 can be used to quantify the radiation dose of the whole body and normal organs of interest. However, as earlier shown with FDG-PET, excessive body weight has negative effects on both quantitative and qualitative scan analysis (27-30). For 89Zr studies these effects may be even more pronounced due to the low positron emission abundance resulting in lower noise equivalent count rates (NECR) than seen with FDG studies. The low NECR could potentially hamper the accuracy and precision of the scatter correction, but further studies are required to fully understand the negative bias seen with heavier patients. Yet the association between patient weight and bias suggests that this effect is indeed related to scatter correction issues. Despite this fact, a good agreement between PET and sample derived blood pool activities was seen for most other scans and subjects (Figure 3). Note that in future studies, with the use of modern PET/CT-scanners in combination with time-of-flight reconstruction and optimalized scan protocols, it is probable that these problems will be of less magnitude, but this would require further validation as well.
Also in the assessment of tumor uptake, a good agreement was found between PET derived data and data obtained from biopsies, despite there was one day difference in assessment time (144 h p.i. versus 168 h p.i.). This good agreement is quite remarkable since both methods are prone to errors. For example, for uptake assessment in tumor biopsies it is difficult to take a representative part of the tumor. For PET assessment, partial volume effects will cause an underestimation of the tumor dose. This problem with partial volume effects is a known limitation of PET and correction methods are currently being developed to deal with this. At this point we can at least identify patients with low and high tumor uptake, respectively, and, therefore, it is possible to select the patients who may and may not benefit from therapy.
Although 89Zr-immuno-PET can become an important tool in the detection and treatment of cancer, there are some limitations to overcome. Drawing of the organ VOI´s requires anatomical knowledge, training, and is time consuming.
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