First-in-human EphA2-targeting PET imaging with the bicyclic radiotracer [⁶⁸Ga]Ga-BCY18469 in pancreatic cancer patients: biodistribution, dosimetry and initial findings.

Abstract

Erythropoietin-producing hepatocellular receptor A2 (EphA2) is overexpressed in various malignancies, including pancreatic ductal adenocarcinoma (PDAC), in which it correlates with poor prognosis. Although EphA2 is considered a promising target receptor for theranostic applications, suitable radiotracers for clinical imaging have been lacking. This study reports first clinical experiences with [⁶⁸Ga]Ga-BCY18469, a bicyclic peptide radiotracer for EphA2-targeted PET imaging. Seven patients with histologically confirmed PDAC (5 after chemotherapy, 2 at initial staging) underwent PET/CT imaging. Four were scanned at 15, 30, 45, 60 and 180 min. and three at 45 min. after injection of [⁶⁸Ga]Ga-BCY18469. Dosimetry calculations were performed based on organ-specific time-activity curves from whole-body PET acquisitions. Imaging findings were compared with contrast-enhanced CT or MRI (interval: 9-50 days). No adverse events were observed. The kidneys received the highest absorbed dose (0.31 ± 0.02 mGy/MBq), while the effective dose was 0.017 ± 0.002 mSv/MBq. [⁶⁸Ga]Ga-BCY18469 demonstrated rapid tumor uptake at 15 min. post-injection with predominantly renal excretion. Of 45 total lesions EphA2-PET detected 36 lesions with tracer uptake suspicious for metastasis. 11 of 45 lesions were detected only on EphA2-PET, whereas 9 of 45 lesions were detected only on CT and/or MRI. The tracer identified 13 liver metastases (SUV_max 6.9 ± 3.4) and 13 lymph node metastases (SUV_max 5.0 ± 1.1), among other findings. Our initial clinical experiences demonstrate that [⁶⁸Ga]Ga-BCY18469 enables safe, rapid, and high-contrast visualization of EphA2-expressing PDAC lesions. These results strongly support further investigation of [⁶⁸Ga]Ga-BCY18469 as a diagnostic tool for EphA2-positive malignancies.