Numerical comparison of iodine-based and indium-based antibody biodistributions.
OBJECTIVE
Single-step iodination is often performed in preference to use of a radiometal label for initial animal biodistributions. Yet loss of iodine occurs in vivo so that it is important to measure uptake (%ID/g) differences between radiolabels.


METHODS
Murine biodistributions of four radioiodinated and (111)In-labeled cognate anti-carcinoembryonic antigen antibodies were compared. Uptakes were obtained in athymic mice out to 96 hours for diabody, minibody, scFv-Fc, and intact humanized (M5A) versions of the T84.66 antibody. Tissues included liver, spleen, kidneys, lungs, and human LS174T colorectal xenografts. Ratios (R) of iodine uptake to indium uptake were calculated.


RESULTS
For all cognates, no significant differences were found in the blood uptakes between the two labels. In normal solid organs, iodine was generally cleared more rapidly with decreasing molecular weight (MW). In liver and spleen by 24 hours, the R value was 5% for diabody and minibody, whereas a value of 50% was seen for the intact mAb. Renal differences were even more marked for the two lower MW species. Tumor losses, however, were found to be essentially independent of MW and were modest; 50% by 48 hours. To test the generality of the results, comparisons were then made for normal organs and tumors of the R values found above for M5A and MN-14 intact antibody literature results. Good agreement, within estimated errors in R, was seen between these two cases, although (111)In and (88)Y were the respective radiometals.


CONCLUSIONS
Loss of iodine from labeled antibodies can be marked in normal organs and that correction (by 1/R) of the iodine biodistribution to estimate the associated radiometal result may be possible. Explicit differences between the two types of biodistribution also imply that separate uptake results need to be considered when evaluating the impact on imaging and therapy using various possible radiolabels.
1 Division of Diagnostic Radiology, City of Hope National Medical Center , Duarte, California.
Lawrence E
LE
Williams
Anna M
AM
Wu
Vania E
VE
Kenanova
Tove
T
Olafsen
Paul J
PJ
Yazaki
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003110:Colonic Neoplasms / Q000378:metabolism; D006801:Humans; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes