194 Objectives Intraoperative imaging can provide valuable information about tumor localization and extent and may thereby facilitate complete tumor resection. This technique may prove particularly valuable if (small) tumors need to be removed that would be difficult to detect with the naked eye. The humanized anti-CEA monoclonal antibody labetuzumab (hMN14) can be used as a tumor-targeting agent in colorectal cancer (CRC), as CEA (carcinoembryonic antigen) is overexpressed in approximately 95% of CRC. Dual-labeled labetuzumab, labeled with both a near-infrared fluorescent dye (IRDye800CW) and a radioactive label (Indium-111), can be used to perform dual-modality imaging. This study aimed to assess whether intraoperative dual-modality imaging using Indium-111-DTPA-labetuzumab-IRDye800CW can detect CEA-expressing pulmonary micrometastases. Methods Pulmonary GW39 microcolonies were induced in athymic BALB/c mice by intravenous injection of 100 µL of a 10% GW39 cell suspension obtained from subcutaneous xenografts. At 4, 11, 18, and 25 days after tumor cell injection mice (n=7 per time point) were injected i.v. with Indium-111-DTPA-labetuzumab-IRDye800CW (10 µg, 25 MBq 111In). Three days later mice were euthanized, the lungs were fixed by intratracheal injection of 4% formalin and then microSPECT/CT images and optical images were acquired. Finally, the biodistribution of the dual-labeled tracer was determined. Formalin fixed sections of the lungs were analyzed using fluorescence imaging, autoradiography and immunohistochemistry. Results Submillimeter pulmonary tumor colonies could be visualized with both microSPECT and fluorescence imaging from the first week of tumor growth, before they became visible with the naked eye. After three weeks of tumor growth pulmonary tumors could be resected by using fluorescence imaging. Mean uptake of the dual-labeled tracer in tumor nodules was 17.2 ± 5.4 %ID/g and 17.0 ± 8.3 %ID/g in week 3 and 4 respectively. Immunohistochemical analysis of the tumorous lungs showed that the distribution of the radioactive and fluorescent signal co-localized with CEA-expressing tumor nodules. Conclusions Dual-modality imaging after injection of Indium-111-labetuzumab-IRDye800CW can be used to detect submillimeter CEA-expressing pulmonary colonies, before they become visible with the naked eye. A clinical study will be initiated to evaluate the feasibility of CEA-targeted intraoperative dual-modality imaging in CRC patients with peritoneal carcinomatosis scheduled for cytoreductive surgery and HIPEC.

100 Deals associated with Indium-111-DTPA-Labetuzumab-IRDye800CW(Immunomedics, Inc.)

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Indication	Highest Phase	Country/Location	Organization	Date
Lung Cancer	Phase 2	-	Radboud University Nijmegen	-
Lung Cancer	Phase 2	-	Immunomedics, Inc.	-

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