RT Journal Article
SR Electronic
T1 Pharmacokinetics, Biodistribution, and Radiation Dosimetry for <sup>89</sup>Zr-Trastuzumab in Patients with Esophagogastric Cancer
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 161
OP 166
DO 10.2967/jnumed.117.194555
VO 59
IS 1
A1 O'Donoghue, Joseph A.
A1 Lewis, Jason S.
A1 Pandit-Taskar, Neeta
A1 Fleming, Stephen E.
A1 Schöder, Heiko
A1 Larson, Steven M.
A1 Beylergil, Volkan
A1 Ruan, Shutian
A1 Lyashchenko, Serge K.
A1 Zanzonico, Pat B.
A1 Weber, Wolfgang A.
A1 Carrasquillo, Jorge A.
A1 Janjigian, Yelena Y.
YR 2018
UL http://jnm.snmjournals.org/content/59/1/161.abstract
AB Trastuzumab with chemotherapy improves clinical outcomes in patients with human epidermal growth factor receptor 2 (HER2)–positive esophagogastric adenocarcinoma (EGA). Despite the therapeutic benefit, responses are rarely complete, and most patients develop progression. To our knowledge, this is the first report evaluating 89Zr-trastuzumab in HER2-positive EGA; here, we evaluate the safety, pharmacokinetics, biodistribution, and dosimetry 89Zr-trastuzumab. Methods: Trastuzumab was conjugated with deferoxamine and radiolabeled with 89Zr. A mean activity of 184 MBq was administered to 10 patients with metastatic HER2-positive EGA. PET imaging, whole-body probe counts, and blood draws were performed to assess pharmacokinetics, biodistribution, and dosimetry. Results: No clinically significant toxicities were observed. At the end of infusion, the estimated 89Zr-trastuzumab in plasma volume was a median 102% (range, 78%–113%) of the injected dose. The median biologic half-life T1/2β was 111 h (range, 78–193 h). The median biologic whole-body retention half-life was 370 h (range, 257–578 h). PET images showed optimal tumor visualization at 5–8 d after injection. The maximum tumor SUV ranged from no to minimal uptake in 3 patients to a median of 6.8 (range, 2.9–22.7) for 20 lesions in 7 patients. Dosimetry estimates from OLINDA showed that the organs receiving the highest absorbed doses were the liver and heart wall, with median values of 1.37 and 1.12 mGy/MBq, respectively. Conclusion: 89Zr-trastuzumab imaging tracer is safe and provides high-quality images in patients with HER2-positive EGA, with an optimal imaging time of 5–8 d after injection.