title: Quantitative serial imaging of an 124I anti-CEA monoclonal antibody in tumor-bearing mice.
abstract: OBJECTIVE
  The 4.2-day half-life of (124)I favors its use for positron emission tomography (PET) of monoclonal antibodies (mAbs). However, high positron energy and beta(+) -associated cascade gamma rays pose image resolution and background noise problems for (124)I. This study evaluated quantitative PET of an (124)I mAb in tumor-bearing mice.
  
  
  METHODS
  An R4 microPETtrade mark (Siemens/CTIMI, Knoxville, TN) was used with standard energy and coincidence timing windows (350-750 keV and 6 ns, respectively), delayed random coincidence subtraction, iterative image reconstruction, and no attenuation or scatter correction. Image resolution, contrast, and response linearity were compared for (124)I and (18)F, using phantoms. Nude mice bearing human colon tumors (LS-174T) were injected intravenously with a chimeric (124)I anti-CEA mAb (cT84.66) and imaged serially 1 hour to 7 days postinjection. Venous blood was sampled to validate image-derived blood curves. Mice were sacrificed after the final scan, and the biodistribution of (124)I was measured by direct tissue assay. Images were converted to units of kBq/g for each tissue of interest by comparing the final scans with the direct assays.
  
  
  RESULTS
  Measured resolution (FWHM) 0-16 mm from the scanner axis was 2.3-2.7 mm for (124)I versus 1.9-2.0 mm for (18)F. Due to true coincidence events between annihilation photons and cascade gamma rays, background was greater for (124)I than (18)F, but the signal-to-background ratio was still more than 20, and (124)I image intensities varied linearly with activity concentration. Tissue-based calibration worked well (i.e., PET blood curves agreed with direct measurements within 12% at all time points), while calibration, based on a cylindrical phantom approximating the mouse body, yielded tumor quantitation that was 46%-66% low, compared with direct assay.
  
  
  CONCLUSIONS
  Images of quantitative accuracy sufficient for biodistribution measurements can be obtained from tumor-bearing mice by using (124)I anti-CEA mAbs with standard microPET acquisition and processing techniques, provided the calibration is based on the direct assay of excised tissue samples.
authors.affiliation: Department of Radioimmunotherapy, City of Hope, Duarte, CA 91010-3000, USA. jbading@coh.org
authors.forename: James R
authors.initials: JR
authors.lastname: Bading
authors.forename: Magnus
authors.initials: M
authors.lastname: Hörling
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Williams
authors.forename: David
authors.initials: D
authors.lastname: Colcher
authors.forename: Andrew
authors.initials: A
authors.lastname: Raubitschek
authors.forename: Sven E
authors.initials: SE
authors.lastname: Strand
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007457:Iodine Radioisotopes / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D019047:Phantoms, Imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes
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