Pre-clinical and clinical studies of two new bifunctional chelating agents for immunoscintigraphy with 111in-anti-cea monoclonal antibody

A. Faivre-Chauvet, A. Chetanneau, M. Bardiès, C. Sai-Maurel, J. F. Chatal, J. F. Gestin, R. C. Mease, G. E. Meinken, S. C. Srivastava

Research output: Contribution to journalArticlepeer-review

Abstract

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-l,2-diaminocyclohexane tetraacetic acid (CDTA), the monolithium salt of N-[methyl(2-isothiocyanatoethyl)carbamide] trans-l,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 111In-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 111 to localize recurrences (especially in liver) in humans using a one-step targeting method.

Original languageEnglish (US)
Pages (from-to)781-789
Number of pages9
JournalNuclear medicine communications
Volume17
Issue number9
DOIs
StatePublished - Sep 1996
Externally publishedYes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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