Quantitative serial imaging of an 124I anti-CEA monoclonal antibody in tumor-bearing mice

Objective: The 4.2-day half-life I-124 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 I-124. This study evaluated quantitative PET of an I-124 mAb in tumor-bearing mice. Methods: An R4 microPET (TM) (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 I-124 and F-18, using phantoms. Nude mice bearing human colon tumors (LS-174T) were injected intravenously with a chimeric I-124 anti-CEA mAb (cT84.66) and imaged serially 1 hour to 7 clays postinjection. Venous blood was sampled to validate image-derived blood curves. Mice were sacrificed after the final scan, and the biodistribution of I-124 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 I-124 versus 1.9-2.0 mm for F-18. Due to true coincidence e vents between annihilation photons and cascade gamma rays, background was greater for I-124 than F-18, but the signal-to-background ratio was still more than 20, and I-124 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 I-124 anti-CEA mAbs with standard. microPET acquisition and processing techniques, provided the calibration is based on the direct assay of excised tissue samples.