title: PET radioimmunoscintigraphy of renal cell cancer using 89Zr-labeled cG250 monoclonal antibody in nude rats.
abstract: BACKGROUND
  With the introduction of positron-emitting radionuclides with half-lifes in days, such as 89Zr and 124I, radioimmunoscintigraphy (RIS) with positron-emitter-labeled monoclonal antibodies (moAbs) becomes feasible. RIS, using positron emission tomography (immuno-PET), combines the specific localization of an antibody with the high resolution of a PET camera. In the present study, scintigraphic tumor imaging using chimeric moAb G250 labeled with 89Zr (immuno-PET) or 111In (RIS), and [18F]FDG-(PET) was explored in rats with s.c. renal cell carcinoma (RCC) tumors.
  
  
  METHODS
  Nude rats (6-8 rats per group) with s.c. SK-RC-52 tumors were i.v. injected with 4 MBq 111InDTPA-cG250, 20 MBq 89Zr-Df-cG250 or 4 MBq [18F]FDG. Planar 111In-DTPA-cG250 images were obtained 5 minutes, and 24, 48, and 72 hours postinjection (p.i.). 3D PET imaging was performed 5 minutes, and 24, 48, and 72 hours after a 89Zr-Df-cG250 injection and 1 hour after a [18F]FDG injection using a Siemens ECAT EXACT PET camera. Rats were killed after the last imaging session, and the uptake of the radiolabel in the dissected tissues was determined.
  
  
  RESULTS
  Both radiolabeled antibody preparations were stable during 4 days of incubation in serum at 37 degrees C, and the immunoreactivity was preserved. Two (2) days after injection, s.c. tumors (100 mg) were clearly visualized, both with 89Zr-Df-cG250 and 111In-DTPA-cG250. Tumors were not visualized with [18F]FDG (uptake in tumor of 0.5 +/- 0.1 %ID/g, 1 hour p.i.). The biodistribution experiments showed an identical uptake in the tumor for both 89Zr-Df-cG250 and 111In-DTPA-cG250 at 3 days p.i. (5.0 +/- 2.4 and 4.9 +/- 2.9 %ID/g, respectively). Blood levels at 3 days p.i. were also identical (1.4 +/- 0.4 versus 1.7 +/- 0.7 %ID/g), and no significant differences were found in the biodistribution of normal tissues between the two radiolabeled cG250 preparations.
  
  
  CONCLUSIONS
  The cG250 antibody can be stably labeled with the positron-emitter 89Zr, while preserving the immunoreactivity of the moAb. In this rat model, the in vivo biodistribution of 89Zr-Df-cG250 was identical to that of 111In-DTPA-cG250. Immuno-PET of RCC is feasible with 89Zr-cG250, and relatively small tumors could be visualized, even without a dedicated PET camera for small animals.
authors.affiliation: Department of Nuclear Medicine and Urology, University Medical Center Nijmegen, Nijmegen, The Netherlands.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Brouwers
authors.forename: Iris
authors.initials: I
authors.lastname: Verel
authors.forename: Julliëtte
authors.initials: J
authors.lastname: Van Eerd
authors.forename: Gerard
authors.initials: G
authors.lastname: Visser
authors.forename: Martijn
authors.initials: M
authors.lastname: Steffens
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.forename: Frans
authors.initials: F
authors.lastname: Corstens
authors.forename: Wim
authors.initials: W
authors.lastname: Oyen
authors.forename: Guus
authors.initials: G
authors.lastname: Van Dongen
authors.forename: Otto
authors.initials: O
authors.lastname: Boerman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000493:pharmacokinetics; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging*; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007205:Indium Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D007553:Isotope Labeling; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D016719:Radioimmunodetection / Q000379:methods*; D051381:Rats; D011923:Rats, Nude; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays; D015040:Zirconium / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000911:Antibodies, Monoclonal; C106533:G250 monoclonal antibody; D007205:Indium Radioisotopes; D011993:Recombinant Fusion Proteins; D019788:Fluorodeoxyglucose F18; D015040:Zirconium