Pilot study of HER2 targeted 64Cu-DOTA-tagged PET imaging in gastric cancer patients

Matthew C. Hernandez, Paul Yazaki, Joanne E. Mortimer, Dave Yamauchi, Erasmus Poku, Jinha Park, Paul Frankel, Joseph Kim, David M. Colcher, Jeffrey Wong, Yuman Fong, John Shively, Yanghee Woo

Research output: Contribution to journalArticlepeer-review

Abstract

Objective Human epidermal growth factor receptor 2 (HER2) is an important biomarker for targeted gastric cancer (GC) immunotherapy. However, heterogeneous HER2 overexpression in GC, loss of HER2 expression during therapy, and inability to non-invasively identify HER2 overexpressing tumors impede effective targeting therapies. Improved HER2-specific functional imaging can address these challenges. Trastuzumab is a HER2-directed mAb to treat HER2 overexpressing cancers. The 64Cu-DOTA-trastuzumab radiotracer is used to detect HER2+ metastatic breast cancer. We aimed to develop 64Cu-DOTA-trastuzumab PET-CT to detect and characterize tumor uptake in HER2+ or - GC patients. Methods We conducted a single-arm phase II pilot study exploring the feasibility of 64Cu-DOTA-trastuzumab for PET imaging of HER2 overexpressing GC compared to HER2 non-expressing tumors. Eight patients with biopsy-confirmed gastric adenocarcinoma were included. Immunohistochemistry was used to evaluate primary tumor biopsies for HER2 overexpression. Patients were injected with 45 mg of cold trastuzumab followed by 5 mg of 64Cu-DOTA-trastuzumab. PET-CT scans were performed 24-48 h post radiotracer injection and compared to standard staging CT scans. Results We observed limited toxicity following 64Cu-DOTA-trastuzumab injections. While there was uptake of the radiotracer in portions of HER2+ lesions, there was no statistically significant distinction between tumor and background by standardized uptake value analysis. Conclusion Despite the potential of 64Cu-DOTA-trastuzumab PET imaging of HER2+ metastatic breast cancer, a 5 mg dose of this radiotracer injected 24-48 h before imaging was insufficient to identify HER2+ GC. These results inform future GC imaging studies to optimize biomarker-targeted therapies based on dosage and timing for more clinically relevant imaging.

Original languageEnglish
Pages (from-to)1151-1155
Number of pages5
JournalNuclear Medicine Communications
Volume44
Issue number12
DOIs
StatePublished - Dec 1 2023

Bibliographical note

Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.

Keywords

  • Cu
  • DOTA
  • PET
  • gastric cancer
  • immunohistochemistry
  • trastuzumab

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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