Quantitative serial imaging of an 124I anti-CEA monoclonal antibody in tumor-bearing mice.
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.
Bading
James R
JR
Department of Radioimmunotherapy, City of Hope, Duarte, CA 91010-3000, USA. jbading@coh.org
Hörling
Magnus
M
Williams
Lawrence E
LE
Colcher
David
D
Raubitschek
Andrew
A
Strand
Sven E
SE
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
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes
Eur J Nucl Med Mol Imaging. 2007 Sep;34(9):1376-87
17277931
J Nucl Med. 1992 Dec;33(12):2154-60
1460508
Clin Lymphoma. 2004 Oct;5 Suppl 1:S5-10
15498149
Cancer Res. 2002 Oct 15;62(20):5912-9
12384557
Cancer Res. 2005 Feb 15;65(4):1471-8
15735035
Ann Biomed Eng. 2005 Nov;33(11):1640-52
16341929
J Nucl Med. 2001 May;42(5):764-9
11337573
IEEE Trans Med Imaging. 1982;1(2):113-22
18238264
J Nucl Med. 2003 Mar;44(3):457-64
12621015
Eur J Nucl Med Mol Imaging. 2004 Jan;31(1):117-28
14523586
Br J Surg. 2005 Mar;92(3):264-76
15739250
Cancer Res. 1990 Apr 1;50(7):2128-34
2107969
J Nucl Med. 2003 Dec;44(12):1962-9
14660722
Nucl Med Biol. 2006 Feb;33(2):217-26
16546676
J Nucl Med. 1970 Mar;:Suppl 4:7-32
5417950
Bioconjug Chem. 2008 Jan;19(1):89-96
17988078
Immunotechnology. 1998 Jun;4(1):49-57
9661814
Eur J Nucl Med Mol Imaging. 2003 May;30(5):737-47
12536244
J Nucl Med. 1988 Jan;29(1):103-9
3335916
Nucl Med Biol. 2005 Nov;32(8):851-8
16253810
Mol Imaging Biol. 2006 Sep-Oct;8(5):262-77
16897320
Biochem Biophys Res Commun. 1978 Feb 28;80(4):849-57
637870