title: Detection of Micrometastases Using SPECT/Fluorescence Dual-Modality Imaging in a CEA-Expressing Tumor Model.
abstract: Intraoperative dual-modality imaging can help the surgeon distinguish tumor from normal tissue. This technique may prove particularly valuable if small tumors need to be removed that are difficult to detect with the naked eye. The humanized anticarcinoembryonic antigen (anti-CEA) monoclonal antibody, labetuzumab, can be used as a tumor-targeting agent in colorectal cancer, since CEA is overexpressed in approximately 95% of colorectal cancer. Dual-labeled labetuzumab, labeled with both a near-infrared fluorescent dye (IRDye800CW) and a radioactive label (111In), can be used as a tracer for dual-modality imaging. This study aimed to assess whether dual-modality imaging using111In-diethylenetriaminepentaacetic acid (DTPA)-labetuzumab-IRDye800CW can detect pulmonary micrometastases in a mouse model.Methods:Pulmonary GW-39 human colonic carcinoma microcolonies were induced in athymic BALB/c mice by intravenous injection of 100 μL of a GW-39 cell suspension. After 1, 2, 3, and 4 wk of tumor growth, dual-modality imaging was performed 3 d after intravenous injection of111In-DTPA-labetuzumab-IRDye800CW (10 μg, 25 MBq). Small-animal SPECT images and optical images were acquired, and image-guided surgery was performed. 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 small-animal SPECT and fluorescence imaging from the first week of tumor growth, before they became visible to the naked eye. Furthermore, dual-modality imaging could be used to guide resection of tumors. Mean uptake (percentage injected dose per gram) of the dual-labeled tracer in tumors was 17.2 ± 5.4 and 16.5 ± 4.4 at weeks 3 and 4, respectively. Immunohistochemical analysis of the tumorous lungs showed that the distribution of the radioactive and fluorescent signal colocalized with CEA-expressing tumors.Conclusion:Dual-modality imaging after injection of111In-labetuzumab-IRDye800CW can be used to detect submillimeter CEA-expressing pulmonary tumors before they become visible to the naked eye, supporting the added value of this technique in the resection of small tumors.
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands marlene.hekman@radboudumc.nl.|Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands; and.
authors.forename: Marlène C H
authors.initials: MCH
authors.lastname: Hekman
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Rijpkema
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Desirée L
authors.initials: DL
authors.lastname: Bos
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands; and.
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.affiliation: Immunomedics, Inc., Morris Plains, New Jersey.
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands; and.
authors.forename: Peter F A
authors.initials: PFA
authors.lastname: Mulders
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
mesh_terms: D000818:Animals; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D007089:Image Enhancement / Q000379:methods; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D064847:Multimodal Imaging / Q000379:methods; D061206:Neoplasm Micrometastasis / Q000175:diagnosis* / Q000503:physiopathology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D002272:Carcinoembryonic Antigen
keywords: CEA; colorectal cancer; fluorescence-guided surgery; labetuzumab; molecular imaging