RADIOIMMUNODETECTION OF MEDULLARY-THYROID CARCINOMA USING IN-111 BIVALENT HAPTEN AND ANTI-CEA X ANTI-DTPA-INDIUM BISPECIFIC ANTIBODY

Pretargeting labeled bivalent hapten with bispecific antibodies has pr oven feasible in the clinic, and our earlier results have suggested th e technique may be very sensitive for detecting small recurrences and metastases. Medullary thyroid carcinoma (MTC) is an example where this technique may be the most useful since local recurrences and isolated metastases are removed surgically when detected, and thyrocalcitonin provides a specific and sensitive tumor marker. In our current study, we evaluated pretargeted immunoscintigraphy in a larger number of MTC patients. Methods: Anti-carcinoembryonic antigen (CEA) x anti-diethyle netriaminepentaacetic acid (DTPA) indium bispecific antibody and In-11 1-labeled bivalent DTPA hapten were administered sequentially (4-5 day s apart) to 44 patients with elevated circulating calcitonin after res ection of primary MTC, Immunoscintigraphy was performed 2, 5 and 24 hr after hapten injection and, when necessary, at longer time intervals, When available, a handheld gamma probe was used during surgery, Resul ts: Fifteen patients had known tumor sites before immunoscintigraphy. Tumors were imaged in 12 (80%) of these patients, including 3 with liv er metastases. Five unknown tumor sites were detected. For the 29 pati ents with occult disease, immunoscintigraphy detected high-activity up take sites in 21 patients (72%), including 5 in the liver. Twelve were confirmed by surgery, 1 by guided morphologic imaging and 1 by venous catheterization. There were 2 false-positive patients. The other 5 pa tients have not yet been confirmed. All detected liver metastases were high-activity uptake areas. Radioimmunoguided surgery was used in 14 patients. It was considered helpful by the surgeon in 12 patients, inc luding 4 patients where it determined the resection of small, not palp able nor visible, tumor-involved lymph nodes. Surgical resection resul ted in a significant decrease (8 patients) or normalization (1 patient ) of circulating calcitonin and CEA, Conclusion: This technique afford s high sensitivity and specificity for detecting small tumor lesions i ncluding liver metastases, Its use for immunoscintigraphy and guided s urgery should improve the therapeutic management of recurrent MTC.