[68Ga]Ga-BCY18469 PET imaging safely visualizes EphA2-positive pancreatic cancer lesions with high contrast.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, often diagnosed at advanced stages due to a lack of early symptoms, leading to poor prognosis. Current imaging modalities frequently miss smaller or diffuse lesions, hindering accurate staging and treatment planning. The erythropoietin-producing hepatocellular receptor A2 (EphA2) is significantly overexpressed in various aggressive cancers, including PDAC, where its presence correlates with poor outcomes. EphA2 represents a promising theranostic target, but effective clinical radiotracers for its non-invasive imaging have been critically lacking, limiting the translation of EphA2-targeted therapies.

This first-in-human study enrolled 7 patients with histologically confirmed PDAC (5 after chemotherapy, 2 at initial staging). Patients received intravenous injections of [68Ga]Ga-BCY18469. Four patients underwent dynamic PET/CT scans at 15, 30, 45, 60, and 180 min post-injection, while three were scanned at 45 min. Dosimetry calculations were performed using organ-specific time-activity curves from whole-body PET acquisitions. Imaging findings were rigorously compared against standard-of-care contrast-enhanced CT or MRI scans, with an interval of 9-50 days between imaging sessions, to assess diagnostic accuracy and lesion detection.