Page 71 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Initial clinical trials with 89Zr-immuno-PET in oncology
89Zr-trastuzumab-PET for whole body assessment of HER2 target status
Dijkers et al. reported a feasibility study to determine optimal dosage and time of administration of 89Zr-trastuzumab (37 MBq) to enable PET visualization and quantification of tumor lesions in 14 patients with HER2-positive metastatic breast cancer” (22).
Trastuzumab naïve patients who received a total dose of 10 mg trastuzumab
(n=2), showed relatively high liver uptake and pronounced intestinal excretion,
with low blood pool activity, indicating rapid clearance. This rapid clearance was
most probably due to complex formation of trastuzumab with extracellular HER2
domains shed in the plasma. For optimal imaging, trastuzumab naïve patients 4 required a total dose of 50 mg trastuzumab (n=5). This resulted in less liver uptake,
lower intestinal excretion and increased blood pool activity, as illustrated by Figure
1(A) and (B). This dose was considered the optimal dose, as good tumor-to-non-
tumor ratio and favorable biodistribution were observed, although higher doses
were not evaluated due to expected target saturation. Patients already on trastuzumab treatment received a dose of 10 mg trastuzumab. As these patients
(n=7) showed minimal intestinal excretion and slow blood clearance, this was
considered an adequate dose, see Figure 1(C). This study illustrates a dose-
dependent relationship between imaging dose and biodistribution of 89Zr- trastuzumab.
Best timing for evaluation of tumor uptake of 89Zr-trastuzumab was 4-5 days post injection (p.i.) while scans performed at day 6 or 7 p.i. yielded decreased image quality because of insufficient counting statistics. Image quality with 89Zr- trastuzumab-PET was superior to previous 111Indium-labeled-trastuzumab single photon emission computed tomography.
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