Ja. Carrasquillo et al., Similarities and differences in In-111- and Y-90-labeled 1B4M-DTPA antiTacmonoclonal antibody distribution, J NUCL MED, 40(2), 1999, pp. 268-276
Citations number
38
Categorie Soggetti
Radiology ,Nuclear Medicine & Imaging","Medical Research Diagnosis & Treatment
Monoclonal antibodies (MoAb) labeled with Y-90 are being used for radioimmu
notherapy. Because Y-90 is a beta emitter, quantitative information from im
aging is suboptimal. With the concept of a "matched pair" of isotopes, (111
)ln is used as a surrogate marker for Y-90. We evaluated the differences in
biodistribution between (111)ln- and Y-90-labeled murine antiTac MoAb dire
cted against the IL-2R alpha receptor. Methods: The antiTac was conjugated
to the 2-(4-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic a
cid (1B4M-DTPA, also known as MX-DTPA). Nine patients with adult T-cell leu
kemia were treated. Patients received approximately 185 MBq (5 mCi) (111)ln
-labeled antiTac for imaging and 185-555 MBq (5-15 mCi) Y-90-labeled antiTa
c for therapy. The immunoreactivity of (111)ln-labeled antiTac was 90% +/-
6%, whereas for Y-90-labeled antiTac, it was 74% +/- 12%. Results: The diff
erences in blood and plasma kinetics of the two isotopes were small. The ar
ea underneath the blood radioactivity curve was 1.91 percentage +/- 0.58 pe
rcentage injected dose (%ID) x h/mL for (111)ln and 1.86% +/- 0.64 %ID x h/
mL for Y-90. Urinary excretion of Y-90 was significantly greater than that
of (111)ln in the first 24 h (P = 0.001), but later, the excretion of (111)
ln was significantly greater (P = 0.001 to P = 0.04). Core biopsies of bone
marrow showed a mean of 0.0029 +/- 0.0012 %ID/g for (111)ln, whereas the 9
0Y concentration was 0.0049 +/- 0.0021 %ID/g. Analyses of activity bound to
circulating cells showed concentrations of 500- 30,000 molecules of antiTa
c per cell. When cell-bound activity was corrected for immunoreactive fract
ion, the ratio of (111)ln to Y-90 in circulating cells was 1.11 +/- 0.17. T
hree biopsies of tumor-involved skin showed ratios of (111)ln to Y-90 of 0.
7, 0.9 and 1.1. Conclusion: This study shows that differences typically ran
ging from 10% to 15% exist in the biodistribution between (111)ln- and Y-90
-labeled antiTac. Thus, it appears that (111)ln can be used as a surrogate
marker for( 90)Y when labeling antiTac with the 1B4M chelate, although unde
restimates of the bone marrow radiation dose should be anticipated.