Faivre-Chauvet A, Mease R C, Chetanneau A, Bardiès M, Sai-Maurel C, Meinken G E, Srivastava S C, Chatal J F, Gestin J F
INSERM Research Unit 211, Nantes, France.
Nucl Med Commun. 1996 Sep;17(9):781-9. doi: 10.1097/00006231-199609000-00008.
Anti-CEA F(ab')2 monoclonal antibody fragments [F6 MAb F(ab')2] were conjugated to two bifunctional semi-rigid chelating agents derived from trans-1,2-diaminocyclohexane tetraacetic acid (CDTA), the monolithium salt of N-[methyl(2-isothiocyanatoethyl)carbamide] trans-1,2-diaminocyclohexane-N,N',N'-triacetic acid (SCN), and 4 isothiocyanato-trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (4-ICE) and labelled with 111In to obtain IIIIn-labelled-F6 MAb F(ab')2 conjugates (111In-F6-SCN and 111In-F6-4-ICE respectively). Biodistribution in mice and clinical studies were undertaken to assess the potential of these two ligands in the detection of colorectal adenocarcinoma recurrences and metastases in humans. Toxicity studies were carried out on guinea pigs and Swiss mice injected with a dose proportionally 100 times greater than that used in human studies. Clinical studies were performed in patients with clinically and/or biologically suspected adenocarcinoma recurrences. No immunoconjugate-induced toxicity was found. The biodistribution studies in mice gave better visualization of tumour sites with 111In-F6-SCN and 111In-F6-4-ICE than with 111In-F6-DTPA. Ten patients were included in the clinical protocol. 111In-F6-SCN and 111In-F6-4-ICE effectively visualized adenocarcinoma recurrences. However, in this small series, 111In-F6-4-ICE performed somewhat better than 111In-F6-SCN. The present study has demonstrated the potential of new bifunctional semi-rigid chelating agents coupled to antibody and labelled with 111In to localize recurrences (especially in liver) in humans using a one-step targeting method.
抗癌胚抗原F(ab')2单克隆抗体片段[F6单克隆抗体F(ab')2]与两种源自反式-1,2-二氨基环己烷四乙酸(CDTA)的双功能半刚性螯合剂、N-[甲基(2-异硫氰酸根合乙基)脲]反式-1,2-二氨基环己烷-N,N',N'-三乙酸的单锂盐(SCN)以及4-异硫氰酸根合反式-1,2-二氨基环己烷-N,N,N',N'-四乙酸(4-ICE)偶联，并用111铟标记以获得111铟标记的F6单克隆抗体F(ab')2偶联物(分别为111铟-F6-SCN和111铟-F6-4-ICE)。在小鼠身上进行了生物分布研究，并开展了临床研究，以评估这两种配体在检测人类结直肠癌复发和转移方面的潜力。对豚鼠和瑞士小鼠进行了毒性研究，注射剂量按比例比人体研究中使用的剂量大100倍。对临床和/或生物学上怀疑有腺癌复发的患者进行了临床研究。未发现免疫偶联物诱导的毒性。小鼠体内的生物分布研究表明，与111铟-F6-二乙三胺五乙酸相比，111铟-F6-SCN和111铟-F6-4-ICE能更好地显示肿瘤部位。10名患者被纳入临床方案。111铟-F6-SCN和111铟-F6-4-ICE有效地显示了腺癌复发情况。然而，在这个小样本系列中，111铟-F6-4-ICE的表现略优于111铟-F6-SCN。本研究证明了新型双功能半刚性螯合剂与抗体偶联并用111铟标记，采用一步靶向方法在人体中定位复发灶(尤其是肝脏中的复发灶)的潜力。
