PT - JOURNAL ARTICLE AU - Melissa Amy Lumish AU - Steven B. Maron AU - Viktoriya Paroder AU - Joanne F. Chou AU - Marinela Capanu AU - Steven Philemond AU - Joseph A. O'Donoghue AU - Heiko Schöder AU - Jason S. Lewis AU - Serge K. Lyaschenko AU - Neeta Pandit-Taskar AU - Yelena Y. Janjigian TI - Noninvasive assessment of human epidermal growth factor receptor 2 (HER2) in esophagogastric cancer using <sup>89</sup>Zr-trastuzumab PET: a pilot study AID - 10.2967/jnumed.122.264470 DP - 2022 Nov 01 TA - Journal of Nuclear Medicine PG - jnumed.122.264470 4099 - http://jnm.snmjournals.org/content/early/2022/11/23/jnumed.122.264470.short 4100 - http://jnm.snmjournals.org/content/early/2022/11/23/jnumed.122.264470.full AB - Variations in HER2 expression between the primary tumor and metastases may contribute to drug resistance in HER2-positive metastatic esophagogastric cancer (mEGC). 89Zr-trastuzumab positron emission tomography (HER2 PET) holds promise for noninvasive assessment of variations in HER2 expression and target engagement. The aim of this study is to describe HER2 PET findings in patients with mEGC. Methods: Patients with HER2-positive mEGC were imaged with HER2 PET, 18F-fluorodeoxyglucose PET (FDG PET), and computed tomography (CT). Lesions were annotated using measurements (on CT) and maximum standardized uptake values (on HER2 PET). Correlation of visualized disease burden among imaging modalities with clinical and pathologic characteristics was performed. Results: Thirty-three patients with HER2+ mEGC were imaged with HER2 PET and CT (12% esophageal, 64% gastroesophageal junction, and 24% gastric adenocarcinoma), 26 of whom were also imaged with FDG PET. More lesions were identified on FDG PET (median, 7 [range, 1-14]) than HER2 PET (median, 4 [range, 0-11]). Of the 8 lesions identified on HER2 but not FDG PET, 3 (38%) were in bone and 1 was in the brain. Of the 68 lesions identified on FDG but not HER2 PET, 4 (6%) were in bone and the remainder were in the lymph nodes (35, 51%) and liver (16, 24%). Of the 33 total patients, 23 (70%) were HER2 imaging positive (&gt;50% of tumor load positive). Only 10 patients had 100% of the tumor load positive; 2 had 0% positive. When only patients receiving HER2-directed therapy as first-line treatment were considered (n = 13), median progression-free survival (m-PFS) therapy was not significantly different between HER2 imaging-positive and -negative patients. Median PFS for patients with at least one intense or very intense lesion (standardized uptake value ≥10) was 16 [95% CI: 11-not reached] months (n = 7), compared with 12 [95% CI: 6.3-not reached] months for patients without an intense or very intense lesion (n = 6) (P = 0.35). Conclusion: HER2 PET may identify heterogeneity of HER2 expression and allow assessment of lesions throughout the entire body. A potential application of HER2 PET is noninvasive evaluation of HER2 status including assessment of intra-patient disease heterogeneity not captured by standard imaging or single site biopsies.