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J Nucl Med. 2014 Sep;55(9):1519-24. doi: 10.2967/jnumed.114.142141. Epub 2014 Jun 30.

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

Author information

1
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands mark.rijpkema@radboudumc.nl.
2
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
3
Immunomedics, Inc., Morris Plains, New Jersey; and Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, New Jersey.

Abstract

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.

KEYWORDS:

CEA; MN-14; colorectal cancer; fluorescence imaging; image-guided surgery

PMID:
24982436
DOI:
10.2967/jnumed.114.142141
[Indexed for MEDLINE]
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