Page 72 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 4
Figure 1. Dose-dependent biodistribution and clearance of 89Zr-trastuzumab. Radioactivity in the blood pool and intestinal excretion are indicated by arrows.
(A) Trastuzumab-naïve patient, imaging dose = 10 mg
(B) Trastuzumab-naïve patient, imaging dose = 50 mg
(C) Patient on trastuzumab treatment, imaging dose = 10 mg
Reprinted with permission from “Dijkers, E.C., Oude Munnink, T.H., Kosterink, J.G., Brouwers, A.H., Jager, P.L., de Jong, J.R., et al. (2010). Biodistribution of 89Zr-trastuzumab and PET imaging of HER2- positive lesions in patients with metastatic breast cancer. Clin. Pharmacol. Ther. 87, 586-592. doi: 10.1038/ clpt.2010.12”
89Zr-trastuzumab-PET allowed detection of most of the known lesions and some that had remained unnoticed with conventional imaging. In 6 of the 12 patients not all known lesions were detected. Liver lesions were missed in 3 out of 7 patients, possibly due to the high background activity in normal liver tissue, which is involved in mAb catabolism. Interestingly, while poor penetration of trastuzumab in the brain was expected, in 3 patients brain lesions could be visualized. This might be due to disruption of blood-brain barrier in brain metastasis. A limitation of this study was the lack of biopsies for confirmation of the HER2 status of immuno-PET negative lesions.
Tumor lesions showing no uptake of 89Zr-trastuzumab may be due to suboptimal imaging conditions, as illustrated by a case report of a trastuzumab naïve breast cancer patient (12). 37 MBq trastuzumab (50 mg) was administered and a PET scan was obtained 2 days p.i.. Low blood pool levels and massive uptake of 89Zr-trastuzumab in liver metastases (48% of the injected dose) were observed, as well as intestinal uptake, suggesting intestinal excretion. Known bone metastases were hardly visible and no uptake in the brain lesion was observed. This might be the result of an extensive tumor load and/or soluble HER2, which reduces uptake in other tumor lesions, due to an insufficient amount of trastuzumab. After
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