Quantitative Serial Imaging of an 124I Anti-CEA Monoclonal Antibody in Tumor-Bearing Mice

Publisher Website
Google Scholar
Abstract
Objective: The 4.2-day half-life of 124I favors its use for positron emission tomography (PET) of monoclonal antibodies (mAbs). However, high positron energy and β+ -associated cascade γ rays pose image resolution and background noise problems for 124I. This study evaluated quantitative PET of an 124I mAb in tumor-bearing mice. Methods: An R4 microPET™ (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 124I and 18F, using phantoms. Nude mice bearing human colon tumors (LS-174T) were injected intravenously with a chimeric 124I 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 124I 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 124I versus 1.9–2.0 mm for 18F. Due to true coincidence events between annihilation photons and cascade γ rays, background was greater for 124I than 18F, but the signal-to-background ratio was still more than 20, and 124I 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 124I anti-CEA mAbs with standard microPET acquisition and processing techniques, provided the calibration is based on the direct assay of excised tissue samples.

This publication has 24 references indexed in Scilit: