Development of anti-CD30 radioimmunoconstructs (RICs) for treatment of Hodgkin's lymphoma. Studies with cell lines and animal studies

Comparison of the binding affinity to a CD30-positive Hodgkin lymphoma (HL) cell line and biodistribution in HL bearing mice of new anti-CD30 radioimmunoconjugates (RICs) of varying structure and labelling nuclides. The antibodies Ki-4 and 5F11 were radioiodinated by the chloramine T method or label...

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Bibliographic Details
Published in:	Nuclear medicine Vol. 49; no. 3; p. 97
Main Authors:	Dietlein, Markus, Börner, S M, Fischer, T, Hansen, H, Schnell, R, Zimmermanns, B, Tawadros, S, Engert, A, Staak, O, Pogge von Strandmann, E, Kobe, C, Schicha, H, Schomäcker, K
Format:	Journal Article
Language:	English
Published:	Germany 2010
Subjects:	Animals Antibodies, Monoclonal - immunology Antibodies, Monoclonal - therapeutic use Cell Division Cell Line, Tumor Hodgkin Disease - pathology Hodgkin Disease - radiotherapy Humans Indium Radioisotopes - pharmacokinetics Indium Radioisotopes - therapeutic use Iodine Radioisotopes - pharmacokinetics Iodine Radioisotopes - therapeutic use Ki-1 Antigen - antagonists & inhibitors Ki-1 Antigen - immunology Mice Radiotherapy - adverse effects Radiotherapy Dosage Tissue Distribution
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Summary:	Comparison of the binding affinity to a CD30-positive Hodgkin lymphoma (HL) cell line and biodistribution in HL bearing mice of new anti-CD30 radioimmunoconjugates (RICs) of varying structure and labelling nuclides. The antibodies Ki-4 and 5F11 were radioiodinated by the chloramine T method or labelled with (111)In via p-NCS-Benzyl-DOTA. In addition, the Ki-4-dimer was investigated in the iodinated form. The RICs were analyzed for retained immunoreactivity by immunochromatography. In-vitro binding studies were performed on CD30-positive L540 cell lines. For in-vivo biodistribution studies, SCID mice bearing human HL xenografts were injected with the various radioimmunoconjugates. After 24 h, activities in the organs and tumour were measured for all 5 RICs. Tumour-free animals were studied in the same way with (131)I- Ki-4 24 h p. i. The three RICs with the highest tumour/background ratios 24 h p.i. ((131)I-Ki-4, (131)I-5F11, (111)In-bz-DOTA-Ki-4) were analysed further at 48 h and 72 h. All the RICs were successfully labelled with high specific activities (28-47 TBq/mmol) and sufficient radiochemical yields (>80%). Scatchard plot analysis proved high tumour affinity (KD = 20-220 nmol/l). In-vivo tumour accumulation in % of injected dose per g tissue (%ID/g) lay between 2.6 ((131)I-5F11) and 12.3 % ID/g ((131)I-Ki-4) with permanently high background in blood. Tumour/blood-ratios of all RICs were below one at all time points. In-vitro tumour cell affinities of all RICs were promising. However, in-vivo biokinetics tested in the mouse model did not meet expectations. This highlights the importance of developing and testing further new anti-CD30 conjugates.
ISSN:	0029-5566
DOI:	10.3413/nukmed-0258