Multimodal imaging of Ewing sarcoma in a preclinical model demonstrates the advantage of immunoPET

Objectives Localized Ewing sarcoma has an excellent 5-year event-free survival, but patients with metastatic disease have a poor prognosis. Current imaging methods provide high resolution anatomic data but lack sensitivity and specificity. In this preclinical study, we compared the detection of metastatic Ewing sarcoma using immunoPET with MRI and [¹⁸F]FDG-PET.

Methods Luciferase-transfected TC32 Ewing sarcoma cells were injected into NOD scid gamma mice via the tail vein and monitored for growth by bioluminescence imaging until development of 2-3 mm liver metastases at 4 weeks. Mice were then injected with a ⁸⁹Zr-labeled anti-CD99 antibody and imaged from 16 to 144 h post-injection (p.i.). Prior to immunoPET, the mice were imaged with MRI and [¹⁸F]FDG-PET. At 144 h p.i., the animals were sacrificed and accumulation of the ⁸⁹Zr-labeled antibody in metastases and surrounding liver was measured using autoradiography.

Results Liver metastases were detected by immunoPET from 16 h to 144 h p.i., with the maximum tumor-to-background ratio observed at 72 h p.i. (SUVmax = 12.5 for tumor and 4 for local normal tissues). Liver metastases of 2-3mm diameter were identified on MR images guided by immunoPET data, but were not detected using [¹⁸F]FDG. Autoradiographic data indicated a ratio of ⁸⁹Zr-Ab uptake between metastases and surrounding liver of 13:1.

Conclusions Our ⁸⁹Zr-labeled anti-CD99 Ab probe out-performed [¹⁸F]FDG and MRI in the detection of Ewing sarcoma liver micrometastases, improving on our work with the ⁶⁴Cu-anti-CD99 probe with enhanced tumor-to-background ratios at later time points. The more sensitive and specific detection and monitoring of micrometastatic disease may have tremendous implications for the clinical care of patients with metastatic Ewing sarcoma.