Based on previous experiments in nude mice, showing that fluoresceinated monoclonal antibodies against carinoembryonic antigen localized specifically in human carcinoma xenografts and could be detected by laser-induced fluorescence, we performed a feaibilit study to determine whether this immunopho method could be applied in the clinic. Six patients, with known primary colorectal carcinoma, received an i.v. injection of 4.5 or 9 mg of mousehuman chimeric anti-carcinoembryonic antigen monoclonal antibody coupled with 0.10-0.28 mg offluorescein (molar ratio 1/10 to 1/14). The monoclonal antibody was also labeled with 0.2-0.4 mCi of 12-I (1 Ci = 37 GBq). Photodetection of the tumor was done ex vivo on surgically resected tissues for the six patients and in vivo by fluorescence rectosigmoidoscopy for the sixth patient. Upon laser irradiation, ciearly detectable heterogeneous green fluorescence from the dye-antibody conjugate was visually observed on all six tumors; almost no such fluorescence was detectable on normal mucosa. The yellowish tissue autofluorescence, which was emitted from both tumor and normal mucosa, could be subtracted by real-time image processing. Radioactivity measurements confirmed the specificity of tumor localization by the conjugate; tissue concentrations of up to 0.059% Injected dose per g of tumor and 10 times les (0.006%) per g of normal mucosa were found. The overall results demonstrate the feasibility of tumor immunophotodiagnosis at the clinical level.chlorins, have been coupled to monoclonal antibodies (mAbs), but these conjugates were studied primarily in vitro (6)(7)(8), and the few experimental immunophototherapy studies did not yield highly significant results (9). The obvious advantage of using mAbs as vectors for tumor localization of dyes is the ability of a mAb to bind specifically to an antigen that is more abundant in tumor than in normal tissue. Furthermore, this technique allows selection of the dye on the basis of its photophysical and spectral properties, independently of its weak tumor-localizing properties.We chose human-mouse chimeric mAb directed against carcinoembryonic antigen (CEA) (10) because anti-CEA antibodies have given the best experimental and clinical results for colorectal carcinoma localization (11, 12) and chimeric mAbs were less immunogenic in patients than their murine counterpart (13). We selected fluorescein as the dye, primarily for its favorable photophysical properties, as shown in the innumerable in vitro applications of mAb-fluorescein conjugates and secondly because it can be injected in large doses into patients without side effects (14).We have previously shown that anti-CEA mAb-fluorescein conjugates injected i.v. in nude mice bearing human colon carcinoma xenografts allow clear immunophotodetection of these tumors (15). The purpose of the present pilot clinical trial was to determine whether such type of tumor immunophotodiagnosis is feasible in patients.Despite major progress in understanding the process of malignant transformation ...