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

Bading, James R.; Horling, Magnus; Williams, Lawrence E.; Colcher, David; Raubitschek, Andrew and Strand, Sven-Erik LU (2008) In Cancer Biotherapy & Radiopharmaceuticals 23(4). p.399-409
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
molecular imaging, antibody, cancer, PET, radioimmunotherapy
in
Cancer Biotherapy & Radiopharmaceuticals
volume
23
issue
4
pages
399 - 409
publisher
Mary Ann Liebert, Inc.
external identifiers
  • wos:000259167300002
  • scopus:51349115105
ISSN
1557-8852
DOI
10.1089/cbr.2007.0457
language
English
LU publication?
yes
id
ef02487a-0e6f-400d-b184-f2ce1da28d70 (old id 1247025)
date added to LUP
2008-11-17 11:41:22
date last changed
2017-01-01 06:25:19
@article{ef02487a-0e6f-400d-b184-f2ce1da28d70,
  abstract     = {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.},
  author       = {Bading, James R. and Horling, Magnus and Williams, Lawrence E. and Colcher, David and Raubitschek, Andrew and Strand, Sven-Erik},
  issn         = {1557-8852},
  keyword      = {molecular imaging,antibody,cancer,PET,radioimmunotherapy},
  language     = {eng},
  number       = {4},
  pages        = {399--409},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Cancer Biotherapy & Radiopharmaceuticals},
  title        = {Quantitative serial imaging of an I-124 anti-CEA monoclonal antibody in tumor-bearing mice},
  url          = {http://dx.doi.org/10.1089/cbr.2007.0457},
  volume       = {23},
  year         = {2008},
}