Chetanneau A, Barbet J, Peltier P, Le Doussal J M, Gruaz-Guyon A, Bernard A M, Resche I, Rouvier E, Bourguet P, Delaage M
Department of Nuclear Medicine, Nantes Cancer Center, France.
Nucl Med Commun. 1994 Dec;15(12):972-80. doi: 10.1097/00006231-199412000-00009.
In 11 patients recurrence of colorectal cancer was suspected by a rise in serum carcinoembryonic antigen (CEA) (nine cases), by a subocclusive clinical situation (one case) or by endoscopy (on an anastomosis, one case). Two-step tumour targetting was performed by a first injection of 0.1 mg kg-1 of unlabelled bispecific antibody conjugate (an anti-CEA Fab' fragment chemically coupled to an anti-diethylene triamine pentaacetate (DTPA)-indium fragment) followed 4 to 5 days later by injection of the bivalent DTPA hapten labelled with 5 to 8 mCi 111In. Planar scintigraphy, single photon emission computed tomographic (SPECT) 360 degrees acquisitions and whole-body scans were obtained 4.5 and 24 h after injection of the radiolabelled hapten. Biodistribution was determined for eight patients at 48 h. The final diagnosis was confirmed histologically in nine patients (eight by second-look surgery, one by laparotomy). Overall, results were one true negative (1-year follow-up) and 10 true positive; however, for the three large liver metastases (3 to 6 cm), only the periphery of the metastasis had high uptake compared to normal liver. For pelvic recurrences, immunoscintigraphic (IS) contrast was better for small tumours. The highest tumour uptake was 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 targetting technique, which uses a bispecific antibody conjugate and an 111In-labelled bivalent hapten injected sequentially without chasing the excess bispecific antibody, provided satisfactory results in this preliminary clinical trial for detection of recurrent colorectal cancers.
11例患者中，9例因血清癌胚抗原（CEA）升高、1例因亚闭塞临床情况、1例因内镜检查（吻合口处）怀疑结直肠癌复发。采用两步肿瘤靶向法，先注射0.1 mg/kg未标记的双特异性抗体偶联物（一种化学偶联抗二乙烯三胺五乙酸（DTPA）-铟片段的抗CEA Fab'片段），4至5天后再注射用5至8 mCi 111In标记的二价DTPA半抗原。在注射放射性标记半抗原后4.5小时和24小时进行平面闪烁显像、单光子发射计算机断层扫描（SPECT）360度采集和全身扫描。8例患者在48小时时测定生物分布。9例患者经组织学确诊（8例通过二次探查手术，1例通过剖腹手术）。总体而言，结果为1例假阴性（1年随访）和10例假阳性；然而，对于3个大的肝转移灶（3至6 cm），与正常肝脏相比，仅转移灶周边摄取高。对于盆腔复发，小肿瘤的免疫闪烁显像（IS）对比度更好。直径1 cm的盆腔复发灶摄取最高（7.2% i.d. kg-1）。平均肿瘤与血液比值为6.4。因此，这种两步肿瘤靶向技术，使用双特异性抗体偶联物和111In标记的二价半抗原依次注射，无需清除过量的双特异性抗体，在这项检测复发性结直肠癌的初步临床试验中取得了满意的结果。
