Synapse - Pharmacokinetics, biodistribution, and radiation dosimetry for (89)Zr-trastuzumab in patients with esophagogastric cancer

Pharmacokinetics, biodistribution, and radiation dosimetry for (89)Zr-trastuzumab in patients with esophagogastric cancer Journal Article

Authors:	O'Donoghue, J. A.; Lewis, J. S.; Pandit-Taskar, N.; Fleming, S. E.; Schöder, H.; Larson, S. M.; Beylergil, V.; Ruan, S.; Lyashchenko, S. K.; Zanzonico, P. B.; Weber, W. A.; Carrasquillo, J. A.; Janjigian, Y. Y.
Article Title:	Pharmacokinetics, biodistribution, and radiation dosimetry for (89)Zr-trastuzumab in patients with esophagogastric cancer
Abstract:	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-posi-tive 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 T1/2b 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. COPYRIGHT © 2018 by the Society of Nuclear Medicine and Molecular Imaging.
Keywords:	adult; clinical article; aged; drug safety; prospective study; cohort analysis; chill; drug distribution; isotope labeling; image quality; paracetamol; radiation measurement; drug half life; trastuzumab; esophageal adenocarcinoma; stomach adenocarcinoma; zirconium 89; drug excretion; deferoxamine; esophageal cancer; her2; gastric cancer; diphenhydramine; 89zr; radiation absorption; plasma volume; human; male; female; priority journal; article; positron emission tomography-computed tomography
Journal Title:	Journal of Nuclear Medicine
Volume:	59
Issue:	1
ISSN:	0161-5505
Publisher:	Society of Nuclear Medicine
Date Published:	2018-01-01
Start Page:	161
End Page:	166
Language:	English
DOI:	10.2967/jnumed.117.194555
PROVIDER:	scopus
PMCID:	PMC5750520
PUBMED:	28637800
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85040089429&doi=10.2967%2fjnumed.117.194555&partnerID=40&md5=7a0880b5637268c1cfa82d50729cc829
Notes:	Article -- Export Date: 1 February 2018 -- Source: Scopus