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Nuklearmedizin 1988; 27(03): 87-94
DOI: 10.1055/s-0038-1629439
Review Articles
Schattauer GmbH

Radioiodination of Murine Anti-Alphafoetoprotein E.9 Monoclonal Antibody and its F(ab’)2 Fragment for the Diagnosis of Hepatocellular Carcinoma

M. Beyers
1   From the Atomic Energy Corporation of South Africa, Pinetown, South Africa
,
S. Aspinall
2   From the Pretoria, the Medical University of Southern Africa, Pinetown, South Africa
,
J. D. Conradie
3   Pretoria and the Natal Institute for Immunology, Pinetown, South Africa
,
P. J. Fourie
1   From the Atomic Energy Corporation of South Africa, Pinetown, South Africa
› Institutsangaben
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Publikationsverlauf

Received: 04. November 1987

Publikationsdatum:
04. Februar 2018 (online)

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The high incidence of hepatocellular carcinoma amongst certain population groups of Southern Africa made feasible the investigation of a radiolabeled monoclonal anti-alphafoetoprotein as a radioimmunodiagnostic agent for this disease. This paper reports the preclinical trials with monoclonal anti-alphafoetoprotein E.9 (anti-AFP) and its F(ab’)2 fragment after radiolabelling with 131l. Various radioiodinations were tried. The best results were obtained with the lodogen and Bolton-Hunter methods.1311 from only one of the sources tested gave an 131 l-labelled anti-AFP with meaningful immunoreactivity. It was shown by means of gamma-camera scans and monitoring of radioactivity in individual organs that 131l-anti-AFP and the 131l-anti-AFP F(ab’)2 fragments did not accumulate abnormally in any organ(s) in healthy animals. The correlation in healthy mice of the biodistribution of 125l human IgG to 131 l-anti-AFP, and 125l human IgG to 131l-F(ab’)2 was good. Human hepatoma xenografts in athymic mice showed uptake of131 l-anti-AFP and the 131l-F(ab’)2 fragment. The uptake of 131l-F(ab’)2 was improved by liver background subtraction. There was correlation between circulatory alphafoetoprotein concentrations and tumour uptake of 131l-F(ab’)2 in tumour-bearing athymic mice and a definite relationship was found between tumour size and radiolabelled antibody and the F(ab’)2 fragment. After the biological action of the131 l-anti-AFP and the 131l-F(ab’)2 fragment was known, sterile pyrogen-free consignments were supplied for clinical trials in humans on a regular basis.

Zusammenfassung

Die hohe Inzidenz des hepatozellulärenKarzinoms unter bestimmtenBevölkerungsgruppen des südlichenAfrika ließ die Untersuchung von radioaktivmarkiertem monoklonalemAntialphafetoprotein als Radioimmundiagnostikumfür diese Erkrankungsinnvoll erscheinen. In dieserArbeit wird über präklinische Versuchemit monoklonalem AntialphafetoproteinE.9 (Anti-AFP) und seinesF(ab’)2-Fragments nach Markierungmit 131J berichtet. Verschiedene Methodender Radiojodierung wurdengetestet. Die besten Ergebnisse wurdenmit der Jodogen-Methode unddem Bolton-Hunter-Verfahren erreicht.131J verschiedener Herstellerwurde getestet. Nur 131J aus einer dergeprüften Quellen ergab eine 131J-Anti-AFP-Markierung mit brauchbarerImmunreaktivität. Mit Hilfe vonGamma-Kamera-Szintigrammen undmit Radioaktivitätsmessungen in einzelnenOrganen wurde gezeigt, daß131J-Anti-AFP und das 131J-Anti-AFPF(ab’)2-Fragment sich in keinemOrgan gesunder Tiere abnormal anreicherte.Die Korrelation der Bioverteilungvon 125J-markiertem humanemund mit 125J-markiertem humanemIgG zu 131J-markiertem F(ab’)2 war ingesunden Mäusen gut. MenschlicheHepatom-Xenotransplantationen inathymischen Mäusen zeigten eine Anreicherungdes 131J-markierten Anti-AFP und des 131J-F(ab’)2-Fragments.Die Aufnahme des 131J-F(ab’)2 wurdenach Leberhintergrundsubtraktionbesser dargestellt. Eine Abhängigkeitzwischen Blutalphafetoproteinkonzentrationund dem Tumoruptake von131J-F(ab’)2 in tumortragenden Nacktmäusenund ein bestimmter Zusammenhangzwischen der Tumorgrößeund dem radioaktiv markierten Antikörperund dem F(ab’)2-Fragmenwurde nachgewiesen. Nachdem diebiologische Wirkung des 131J-Anti-AFP und des 131J-F(ab’)2-Fragmentsbekannt war, wurden sterile pyrogenfreieChargen für klinische Prüfungenam Menschen regelmäßig hergestellt.

 

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