title: ImmunoPET imaging of renal cell carcinoma with (124)I- and (89)Zr-labeled anti-CAIX monoclonal antibody cG250 in mice.
abstract: BACKGROUND
  Monoclonal antibody (mAb) cG250 recognizes carbonic anhydrase IX (CAIX), overexpressed on clear cell renal cell carcinoma (ccRCC). (124)I-cG250 is currently under clinical investigation for the detection of ccRCC. However, the (124)I label is rapidly excreted from the tumor cells after internalization of the radiolabeled mAb. We hypothesized that labeling cG250 with the residualizing positron emitter (89)Zr would lead to higher tumor uptake and more sensitive detection of ccRCC lesions.
  
  
  METHODS
  Nude mice with CAIX-expressing ccRCC xenografts (SK-RC-52 or NU-12) were i.v. injected with (89)Zr-cG250 or (124)I-cG250. To determine specificity of (89)Zr-cG250 uptake in ccRCC, one control group was i.v. injected with (89)Zr-MOPC21 (irrelevant mAb). PET images were acquired using a small animal PET camera and the biodistribution of the radiolabeled mAb was determined.
  
  
  RESULTS
  The ccRCC xenografts were clearly visualized after injection of (89)Zr-cG250 and (124)I-cG250. Tumor uptake of (89)Zr-cG250 was significantly higher compared with (124)I-cG250 in the NU-12 tumor model (114.7% ± 25.2% injected dose per gram (%ID/g) vs. 38.2 ± 18.3%ID/g, p=0.029), but in the SK-RC-52 the difference in tumor uptake was not significant (48.7 ± 15.2%ID/g vs. 32.0 ± 22.9%ID/g, p=0.26). SK-RC-52 tumors were not visualized with (89)Zr-MOPC21 (tumor uptake 3.0%ID/g). Intraperitoneal SK-RC-52 lesions as small as 7 mm(3) were visualized with (89)Zr-cG250 PET.
  
  
  CONCLUSIONS
  ImmunoPET imaging with cG250 visualized s.c. and i.p. ccRCC lesions in murine models. This confirms the potential of cG250 immunoPET in the diagnosis and (re)staging of ccRCC. PET imaging of ccRCC tumors with (89)Zr-cG250 could be more sensitive than (124)I-cG250-PET.
authors.affiliation: Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Stillebroer
authors.forename: Gerben M
authors.initials: GM
authors.lastname: Franssen
authors.forename: Peter F A
authors.initials: PF
authors.lastname: Mulders
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.forename: Guus A M S
authors.initials: GA
authors.lastname: van Dongen
authors.forename: Peter
authors.initials: P
authors.lastname: Laverman
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000276:immunology; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes / Q000008:administration & dosage; D019275:Radiopharmaceuticals / Q000276:immunology; D015040:Zirconium / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; C106533:G250 monoclonal antibody; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D015040:Zirconium; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C492796:Car9 protein, mouse