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Intraoperative Immunophotodetection for Radical Resection of Cancers

Evaluation in an Experimental Model¹

Department of Oncologic and Reconstructive Surgery [M. G., B. S-A., P. R.], JE2176 Université Montpellier I, Cancer Research Center [M. C., A. P.], and Department of Pathology [D. P.], Cancer Institute Val d’Aurelle—Paul Lamarque, Montpellier, Cedex 5, France, and INSERM U128, Montpellier 34000, France [C. L.]

The aim of our study was to assess the technique of immunophotodetection (IPD) in intraoperative situations in an experimental model and to determine its capacity to detect very small tumor masses. IPD is a recent technology involving fluorescent dye-labeled monoclonal antibodies (MAbs) directed against tumor-associated antigens. Up to now, no intraoperative device for IPD has been developed, and limits of detection of the technique are unknown. MAb-dye conjugates were prepared using the anti-carcinoembryonic antigen MAb 35A7 labeled with indocyanine and ¹²⁵I. Time-dependent (6, 12, 24, 48, and 96 h post i.v. injection) and dose-dependent (10, 40, and 100 µg of conjugate) biodistribution studies were performed in nude mice bearing an LS174T peritoneal carcinomatosis demonstrating high tumor uptake (up to 21% of the injected dose/g of tumor 48 h postinjection). Intraoperative IPD was studied, using a newly developed device, in 16 mice 48 h after i.v. injection of 40 µg of the ¹²⁵I-MAb 35A7-indocyanine conjugate. The fluorescent status of 333 biopsies was compared with their histological analysis. Sensitivity was 90.7%, specificity was 97.2%, the positive predictive value was 94.7%, and the negative predictive value was 94.9%. Detection of very small nodules (<1 mg in weight or <1 mm in diameter) was possible. However, we observed a decrease in sensitivity as a function of tumor mass: 100% for nodules >10 mg versus 78% for nodules 1 mg. These experiments demonstrate that intraoperative IPD is easy to use and associated with high sensitivity and specificity, even for low tumor masses. On the basis of these encouraging results, intraoperative IPD should be assessed in a clinical study.