Immuno-PET of human colon xenograft- bearing BALB/c nude mice using 124I-CDR-grafted humanized A33 monoclonal antibody.
Radiolabeling monoclonal antibodies (mAbs) allows the evaluation of biodistribution of constructs in vivo through gamma camera imaging and also permits quantitation of mAb uptake in tumors through biopsy-based counting techniques. The quantitation of radiolabeled mAb uptake in cancer patients is complicated by the attenuation of gamma emissions of routinely used isotopes (e.g., 131I and 111In) and the spatial resolution and sensitivity of gamma cameras.


METHODS
We used the positron-emitting isotope 124I (half-life [T1/2] = 4.2 d) to label the recombinant humanized anti-colorectal cancer A33 antibody (huA33) and evaluated its biodistribution properties and PET imaging characteristics in BALB/c nude mice bearing SW1222 colorectal xenografts and control colon tumors.


RESULTS
The immunoreactivity of radioconjugate was 78% as determined using the cell-binding Lindmo assay. The apparent association constant was found to be 2.2 x 10(9) M(-1), and the number of antibody binding sites per cell was 371,000. The radioconjugate was found to be stable in serum obtained from mice at various times after injection. Assuming a two-compartment model with a four-parameter fit of mean blood levels, the T1/2alpha was 1.5 h and the T1/2beta was 38.2 h. Excellent tumor uptake was obtained, with maximal uptake reaching 50.0 +/- 7.0 percentage injected dose per gram of tumor by 4 d after injection. Specificity of localization was shown by lack of uptake in control tumor. PET imaging detected antigen-positive tumor by 4 h after injection, and high-resolution images were obtained by 24 h after injection.


CONCLUSIONS
In clinical trials using PET, huA33 labeled with 124I has potential for imaging and staging colon tumors and quantifying antibody uptake in colon tumors in vivo.
Lee
F T
FT
Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research, and Centre for PET, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia.
Hall
C
C
Rigopoulos
A
A
Zweit
J
J
Pathmaraj
K
K
O'Keefe
G J
GJ
Smyth
F E
FE
Welt
S
S
Old
L J
LJ
Scott
A M
AM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D000951:Antigens, Neoplasm / Q000276:immunology; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection; D011994:Recombinant Proteins / Q000276:immunology / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C104258:GPA33 protein, human; C504395:Gpa33 protein, mouse; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins