PRETARGETED IMAGING OF COLORECTAL-CANCER RECURRENCES USING AN IN-111-LABELED BIVALENT HAPTEN AND A BISPECIFIC ANTIBODY CONJUGATE

In 11 patients recurrence of colorectal cancer was suspected by a rise in serum carcinoembryonic antigen (CEA) (nine cases), by a subocclusi ve clinical situation (one case) or by endoscopy (on an anastomosis, o ne case). Two-step tumour targetting was performed by a first injectio n of 0.1 mg kg(-1) of unlabelled bispecific antibody conjugate (an ant i-CEA Fab' fragment chemically coupled to an anti-diethylene triamine pentaacetate (DTPA)-indium fragment) followed 4 to 5 days later by inj ection of the bivalent DTPA hapten labelled with 5 to 8 mCi In-111. Pl anar scintigraphy, single photon emission computed tomographic (SPECT) 360 degrees acquisitions and whole-body scans were obtained 4.5 and 2 4 h after injection of the radiolabelled hapten. Biodistribution was d etermined for eight patients at 48 h. The final diagnosis was confirme d histologically in nine patients (eight by second-look surgery, one b y laparotomy). Overall, results were one true negative (1-year follow- up) and 10 true positive; however, for the three large Liver metastase s (3 to 6 cm), only the periphery of the metastasis had high uptake co mpared to normal liver. For pelvic recurrences, immunoscintigraphic (I S) contrast was better for small tumours. The highest tumour uptake wa s found for a 1 cm diameter pelvic recurrence (7.2% i.d. kg(-1)). Mean tumour-to-blood ratios were 6.4. Thus, this two-step tumour targettin g technique, which uses a bispecific antibody conjugate and an In-111- labelled bivalent hapten injected sequentially without chasing the exc ess bispecific antibody, provided satisfactory results in this prelimi nary clinical trial for detection of recurrent colorectal cancers.