Intraoperative immunophotodetection for radical resection of cancers: Evaluation in an experimental model

The aim of our study was to assess the technique of immunophotodetection (L PD) in intraoperative situations in an experimental model and to determine its capacity to detect very small tumor masses, TPD is a recent technology involving fluorescent dye-labeled monoclonal antibodies (MAbs) directed aga inst tumor-associated antigens. Up to now, no intraoperative device for TPD has been developed, and limits of detection of the technique are unknown. MAb-dye conjugates were prepared using the anti-carcinoembryonic antigen MA b 35A7 labeled with indocyanine and I-125. Time-dependent (6, 12, 24, 48, a nd 96 h post i.v. injection) and dose-dependent (10, 40, and 100 pg of conj ugate) biodistribution studies were performed in nude mice bearing an LS174 T peritoneal carcinomatosis demonstrating high tumor uptake (up to 21% of t he injected dose/g of tumor 48 h postinjection), Intraoperative IPD was stu died, using a newly developed device, in 16 mice 48 h after i,v, injection of 40 mug of the I-125-MAb 35A7-indocyanine conjugate, The fluorescent stat us of 333 biopsies was compared with their histological analysis. Sensitivi ty 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 nod ules (<1 mg in weight or <1 mm in diameter) was possible. However, we obser ved a decrease in sensitivity as a function of tumor mass: 100% for nodules > 10 mg versus 78% for nodules less than or equal to1 mg, These experiment s demonstrate that intraoperative TPD is easy to use and associated with hi gh sensitivity and specificity, even for low tumor masses. On the basis of these encouraging results, intraoperative IPD should be assessed in a clini cal study.