Targeted imaging of Ewing sarcoma in preclinical models using a 64Cu-labeled anti-CD99 antibody.
OBJECTIVE
Ewing sarcoma is a tumor of the bone and soft tissue characterized by diffuse cell membrane expression of CD99 (MIC2). Single-site, surgically resectable disease is associated with an excellent 5-year event-free survival; conversely, patients with distant metastases have a poor prognosis. Noninvasive imaging is the standard approach to identifying sites of metastatic disease. We sought to develop a CD99-targeted imaging agent for staging Ewing sarcoma and other CD99-expressing tumors.


METHODS
We identified a CD99 antibody with highly specific binding in vitro and labeled this antibody with (64)Cu. Mice with either subcutaneous Ewing sarcoma xenograft tumors or micrometastases were imaged with the (64)Cu-labeled anti-CD99 antibody and these results were compared with conventional MRI and 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) imaging.


RESULTS
(64)Cu-labeled anti-CD99 antibody demonstrated high avidity for the CD99-positive subcutaneous tumors, with a high tumor-to-background ratio, greater than that demonstrated with FDG-PET. Micrometastases, measuring 1 to 2 mm on MRI, were not detected with FDG-PET but were readily visualized with the (64)Cu-labeled anti-CD99 antibody. Probe biodistribution studies demonstrated high specificity of the probe for CD99-positive tumors.


CONCLUSIONS
(64)Cu-labeled anti-CD99 antibody can detect subcutaneous Ewing sarcoma tumors and metastatic sites with high sensitivity, outperforming FDG-PET in preclinical studies. This targeted radiotracer may have important implications for the diagnosis, surveillance, and treatment of Ewing sarcoma. Similarly, it may impact the management of other CD99 positive tumors.
Authors' Affiliations: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, and Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston Children's Hospital, and Harvard Medical School; Lurie Family Imaging Center, Dana-Farber Cancer Institute; Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School; Department of Pathology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts; and Department of Pediatrics, Columbia University Medical Center, New York.
Allison F
AF
O'Neill
Jason L J
JL
Dearling
Yuchuan
Y
Wang
Tanya
T
Tupper
Yanping
Y
Sun
Jon C
JC
Aster
Monica L
ML
Calicchio
Antonio R
AR
Perez-Atayde
Alan B
AB
Packard
Andrew L
AL
Kung
D000071443:12E7 Antigen; D000818:Animals; D000906:Antibodies; D000918:Antibody Specificity; D015703:Antigens, CD / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000032:analysis*; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes; D004195:Disease Models, Animal; D005434:Flow Cytometry; D064593:Heterografts; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D009367:Neoplasm Staging / Q000379:methods; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012512:Sarcoma, Ewing / Q000000981:diagnostic imaging* / Q000473:pathology
D000071443:12E7 Antigen; D000906:Antibodies; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D003301:Copper Radioisotopes; D019275:Radiopharmaceuticals