title: Development of anti-CD30 radioimmunoconstructs (RICs) for treatment of Hodgkin's lymphoma. Studies with cell lines and animal studies.
abstract: 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.
authors.affiliation: Department for Nuclear Medicine, University of Cologne, 50937 Cologne, Germany. markus.dietlein@uni-koeln.de
authors.forename: Markus
authors.initials: M
authors.lastname: Dietlein
authors.forename: S M
authors.initials: SM
authors.lastname: Börner
authors.forename: T
authors.initials: T
authors.lastname: Fischer
authors.forename: H
authors.initials: H
authors.lastname: Hansen
authors.forename: R
authors.initials: R
authors.lastname: Schnell
authors.forename: B
authors.initials: B
authors.lastname: Zimmermanns
authors.forename: S
authors.initials: S
authors.lastname: Tawadros
authors.forename: A
authors.initials: A
authors.lastname: Engert
authors.forename: O
authors.initials: O
authors.lastname: Staak
authors.forename: E
authors.initials: E
authors.lastname: Pogge von Strandmann
authors.forename: C
authors.initials: C
authors.lastname: Kobe
authors.forename: H
authors.initials: H
authors.lastname: Schicha
authors.forename: K
authors.initials: K
authors.lastname: Schomäcker
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D017730:Ki-1 Antigen