SPECT- and fluorescence image-guided surgery using a dual-labeled carcinoembryonic antigen-targeting antibody.

Abstract

UNLABELLED:

Intraoperative visualization techniques promise to significantly improve the detection and resection of tumors. In this study, we used an anti-carcinoembryonic antigen (CEA) antibody (MN-14) tagged with both a radiolabel ((111)In) and a fluorophore (IRDye 800CW) for radionuclide detection and intraoperative fluorescence imaging, respectively.

METHODS:

For this purpose, we prepared and characterized the dual-labeled antibody (111)In-diethylenetriaminepentaacetic acid (DTPA)-MN-14-IRDye 800CW and performed 4 studies on mice with subcutaneous and intraperitoneal CEA-expressing tumors: a dose escalation study to determine the optimal MN-14 protein dose, a biodistribution study comparing dual-labeled MN-14 and radiolabeled MN-14, a study to determine the optimal time for SPECT and fluorescence imaging after injection of dual-labeled MN-14, and finally a SPECT and fluorescence image-guided surgery study using this dual-labeled antibody.

RESULTS:

The optimal protein dose of dual-labeled MN-14 was 10 μg per mouse, yielding a tumor-to-blood ratio of 3.5 within 72 h. The biodistribution of (111)In-DTPA-MN-14-IRDye 800CW in mice with subcutaneous LS174T tumors showed tumor uptake after 3 d (19.7% ± 17.0% injected dose/g) comparable to that of (111)In-DTPA-MN-14 but higher accumulation in the liver. The optimal time for imaging after administration of the dual-labeled antibody was 2-3 d after injection. Finally, in mice with intraperitoneally growing LS174T tumor nodules that received (111)In-DTPA-MN-14-IRDye 800CW, intraperitoneal tumor nodules could be localized with SPECT imaging after 3 d and subsequently resected using fluorescence image-guided surgery.

CONCLUSION:

Thus, we showed the feasibility for assessment and image-guided resection of CEA antigen-expressing tumors using dual-labeled MN-14. Both radionuclide detection and fluorescence imaging may provide useful information to improve localization of tumors and radical excision of tumor tissue. Because humanized MN-14 (labetuzumab) is available for clinical use, translation to a clinical setting is the next step.

• Authors: Mark Rijpkema, Wim J Oyen, Desiree Bos, Gerben M Franssen, David M Goldenberg, Otto C Boerman
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 55 Issue 9 Pg. 1519-24 (Sep 2014) ISSN: 1535-5667 [Electronic] United States
• PMID: 24982436 (Publication Type: Journal Article)
• Copyright: © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Chemical References

• Carcinoembryonic Antigen
• Indium Radioisotopes

Topics

• Animals
• Carcinoembryonic Antigen (immunology)
• Colorectal Neoplasms (surgery)
• Female
• Indium Radioisotopes
• Mice
• Mice, Inbred BALB C
• Spectrometry, Fluorescence
• Surgery, Computer-Assisted (methods)
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon (methods)