ImmunoPET compared with conventional imaging modalities for the detection of Ewing sarcoma metastases in a preclinical model.

10048 Background: Ewing sarcoma is a solid tumor arising from bone and the soft tissues that affects approximately 250 children and adolescents each year. Localized disease confers a favorable 75% 5-year survival, but the prognosis for metastatic disease remains dismal with only a 20% 5-year survival. The ability to accurately diagnose disease extent is therefore crucial. Conventional imaging modalities provide high-resolution anatomic data but lack specificity. The goal of this preclinical study was to compare the detection of metastatic Ewing sarcoma using a 89Zr-labeled anti-CD99 antibody (Ab) with conventional imaging modalities including MRI and [18F]FDG-PET. Methods: NOD scid gamma mice were injected via tail vein with luciferase-transduced TC32 Ewing sarcoma cells and monitored for tumor growth by bioluminescence imaging until development of 2-3 mm liver metastases at 4 weeks. Disease burden and lesion distribution were assessed by MRI and [18F]FDG-PET. Mice were then injected with the 89Zr-labeled anti-CD99 Ab and imaged from 16 to 144 h post-injection. Results: Liver metastases were detected by immunoPET from 16 h to 144 h post-injection with the maximum tumor-to-background ratio observed at 72 h (SUVmax = 12.5 for tumor and 4 for local normal tissues). Liver metastases of 2-3 mm diameter were identified on MR images guided by immunoPET data, but were not detected using [18F]FDG. Autoradiography data demonstrated a 89Zr-Ab metastases-to-liver uptake ratio of 13:1. Conclusions: The 89Zr-labeled anti-CD99 Ab PET probe out-performed [18F]FDG and MRI in the detection of Ewing sarcoma metastases, validating our prior work with a 64Cu-labeled anti-CD99 probe. The longer half-life of 89Zr allowed imaging at later time points (72 h) than 64Cu yielding a tumor-to-background ratio that was two-fold higher. The more sensitive and specific detection and monitoring of metastatic disease may have tremendous implications for the clinical care of patients with Ewing sarcoma. In light of existing safety data for the imaging of adult solid tumors with 89Zr-labeled Abs, this study supports next steps for translation to pediatrics.