Presenter(s)
J. Y. C. Wong1, S. V. Dandapani1, D. M. Yamauchi2, Y. Liu3, H. M. McGee1, Y. J. Chen1, H. K. Chen4, K. Melstrom5, L. Lai5, E. Poku3, M. Kujawski6, P. Lee7, A. Wu6, P. Yazaki6, P. Frankel8, and J. E. Shively3; 1Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, 2Department of Diagnostic Radiology, City of Hope National Medical Center, Duarte, CA, 3City of Hope, Duarte, CA, 4Department of Radiation Oncology, City of Hope, South Pasadena, CA, 5Department of Surgery, City of Hope National Medical Center, Duarte, CA, 6Department of Immunology and Theranostics, Beckman Research Institute, City of Hope, Duarte, CA, 7City of Hope Radiation Oncology, Irvine, CA, 8Department of Information Sciences, City of Hope National Medical Center, Duarte, CA
Purpose/Objective(s): Prior studies have demonstrated that anti-carcinoembryonic antigen (CEA) monoclonal antibody (M5A) can target CEA-expressing cancers. This pilot study (NCT05245786) evaluates 64Cu-DOTA-M5A PET imaging in patients with locally advanced rectal cancer to assess its impact on detection of disease and the potential for M5A for CEA targeted radiopharmaceutical therapy (RPT) and immunotherapy
Materials/Methods: Patients with biopsy proven cT3-4 with N0 or N+ rectal cancer, or limited M1 disease underwent 64Cu-M5A PET imaging within 4 weeks prior to start of neoadjuvant RT and 6-8 weeks after end of all neoadjuvant therapy and prior to planned surgery. A regional analysis (primary, pelvic nodes, and extra-pelvic) compared CEA scans to standard of care (SOC) CT and MRI imaging, FDG PET (if available), biopsies and surgical findings. Results: 14 patients were imaged with 64Cu-M5A PET (ages 38-76; CEA 1.8-21.1). CEA PET imaging prior to RT identified the primary tumor in 11 patients. For disease involving pelvic nodes, CEA PET imaging was in concordance with SOC imaging in 9 of patients. In 7 of 14 patients CEA scans identified suspicious lesions outside the pelvis; in 2 patients this was confirmed by SOC imaging and biopsy (lung metastases; and a liver metastasis) and in 5 patients PET avid extra-pelvic nodes (para-aortic, left supraclavicular, mediastinal, porta hepatis, and portacaval) were detected and not imaged as part of SOC. 7 patients were imaged post RT and prior to surgery. 4 had radiologic complete response (CR) on CEA scans which correlated with pathologic CR at surgery or with clinical CR on follow-up sigmoidoscopy. 3 patients had positive scans; 1 at the primary site confirmed as residual disease at surgery; and 1 at the primary site, in mediastinal, para-aortic, and pelvic lymph nodes, and a new focus near the hepatic surface with biopsy confirmation of disease at the primary site and liver; and 1 with progression of tumor at the primary site and an avid lung metastases confirmed by FDG PET. Conclusion: 64Cu-M5A PET imaging in patients with advanced rectal cancer shows promise in identifying sites of disease at the primary site and regional lymph nodes, and in identifying extra pelvic disease not seen by SOC imaging. It shows promise in assessing response to neoadjuvant therapy and selection of patients for non-operative management. It warrants further evaluation as a way to complement SOC imaging at initial staging, to select patients for local regional therapy and for non-operative management, and as a future theranostic agent. 225Ac-M5A is also being evaluated for RPT (NCT05204147) and as an M5A-IL2 immunocytokine for targeted immunotherapy (NCT06130826) in combination with EBRT in phase 1 trials. Pre-clinical studies (JNM 2025, 66: 1605) show low doses of EBRT and M5A-RPT prior to M5A-IL2 can significantly increase tumor control and rejection of tumor rechallenges, laying the foundation for this combined modality strategy in a future trial.