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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dietlein
Markus
M
Department for Nuclear Medicine, University of Cologne, 50937 Cologne, Germany. markus.dietlein@uni-koeln.de
Börner
S M
SM
Fischer
T
T
Hansen
H
H
Schnell
R
R
Zimmermanns
B
B
Tawadros
S
S
Engert
A
A
Staak
O
O
Pogge von Strandmann
E
E
Kobe
C
C
Schicha
H
H
Schomäcker
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D002455:Cell Division; D045744:Cell Line, Tumor; D006689:Hodgkin Disease / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017730:Ki-1 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D017730:Ki-1 Antigen