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Radiolabelling of glycosylated MFE-23 :: CPG2 fusion protein (MFECP1) with Tc-99m for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT)

Francis, RJ; Mather, SJ; Chester, K; Sharma, SK; Bhatia, J; Pedley, RB; Waibel, R; ... Begent, RHJ; + view all (2004) Radiolabelling of glycosylated MFE-23 :: CPG2 fusion protein (MFECP1) with Tc-99m for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT). EUR J NUCL MED MOL I , 31 (8) 1090 - 1096. 10.1007/s00259-004-1474-4.

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Abstract

MFECP1 is a glycosylated recombinant fusion protein composed of MFE-23, a high-affinity anti-carcinoembryonic antigen (CEA) single chain Fv (scFv), fused to the enzyme carboxypeptidase G2 (CPG2), and has been constructed for use in antibody-directed enzyme pro-drug therapy (ADEPT). Radiolabelling of glycosylated MFECP1 with technetium-99m was developed for the purpose of determining tumour localisation of MFECP1 in a phase I ADEPT clinical study. The method used was Tc-99m-carbonyl [Tc-99m(H2O)(3)(CO)(3)](+) (abbreviated to TcCO) mediated labelling of Tc-99m to the hexahistidine (His) tag of MFECP1. MFECP1 fusion protein was labelled with TcCO under a variety of conditions, and this was shown to be a relatively simple and robust method. Tissue biodistribution was assessed in a CEA-expressing LS174T (human colon carcinoma) nude mouse xenograft model. Tissues were taken at 1, 4 and 6 h for assessment of distribution of radioactivity and for measurement of CPG2 enzyme levels. The amount of radioactivity retained by the tumour proved to be an accurate estimation of actual measured enzyme activity, indicating that this radiolabelling method does not appear to damage the antibody-antigen binding or the enzyme activity of MFECP1. However, correlation between CPG2 enzyme activity and measured radioactivity in liver, spleen and kidney was poor, indicating retention of radioactivity in non-tumour sites but loss of enzyme activity. The high retention of technetium radioisotope in normal tissues may limit the clinical applicability of this radiolabelling method for MFECP1; however, these results suggest that this technique does have applicability for measuring the biodistribution of His-tagged recombinant proteins.

Type: Article
Title: Radiolabelling of glycosylated MFE-23 :: CPG2 fusion protein (MFECP1) with Tc-99m for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT)
DOI: 10.1007/s00259-004-1474-4
Keywords: Technetium-99m, radiommunodetection, recombinant fusion protein, antibody, carcinoembryonic antigen, SINGLE-CHAIN FV, PRODRUG THERAPY, CLINICAL-APPLICATIONS, COLORECTAL-CARCINOMA, TECHNETIUM, CYSTEINE, COMPLEX, AGENTS, SCFV
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/191749
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