Blood kinetics, tissue distribution, and radioimaging of anti-common
chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody CLL2 in mice
transplanted with cCLLa-bearing human leukemia cells
GB Faguet, JF Agee and JT DiPiro
Cancer Immunology Research, Veterans Administration Medical Center,
Augusta, GA 30910.
The blood kinetics and biodistribution of anti-common chronic lymphatic
leukemia antigen (cCLLa) monoclonal antibody (MoAb) CLL2 were assessed in
mice bearing cCLLa+ tumors. The cCLLa is a 69-Kd glycoprotein antigen
expressed selectively by malignant B cells in human CLL, hairy cell
leukemia (HCL), and prolymphocytic leukemia. Immunoreactive 125I- CLL2 (5
micrograms/mouse, specific activity 4.3 microCi/micrograms) was injected
intravenously in mice bearing HCL-derived EH xenografts, and blood kinetics
and biodistribution were ascertained up to 16 days postinjection.
Radioimages were also obtained up to 72 hours after injecting 10
micrograms/mouse (specific activity 50.1 microCi/micrograms) of 125I-CLL2.
Distinct 125I-CLL2 blood kinetics were observed in EH engrafted compared
with tumor-free mice including: a longer 125I-CLL2 T 1/2 (153 hours v 72
hours), and a considerably greater blood clearance (173 mg/h v 54.7 mg/h)
with biexponential rather than monoexponential configuration; and a greater
volume of antibody distribution (31,483 mg v 5,729 mg). These data suggest
more rapid tissue uptake by grafted tumours. Preferential 125I-CLL2 uptake
by EH tumours relative to normal tissues was observed beginning 24 hours
postinjection (mean ratio, 4.2) with average peak tumor 125I-CLL2 levels of
428.7 pg/mg. 125I-CLL2 uptake selectivity by EH tumor cells was also
supported by: (1) negligible 125I-CLL2 uptake by cCLLa- Molt-4 xenografts
(average 29.1 pg/mg 24 hours postinjection); (2) background uptake of
cCLLa-irrelevant MoAb 131I-LEU1 by CD5- EH xenografts (average 31.4 pg/mg
48 hours postinjection); and (3) by scintigraphy. The EH xenograft mouse
model might be useful to ascertain preclinically the anti-tumor effect of
anti-cCLLa MoAbs and of their conjugated derivatives.
Volume 75,
Issue 9,
pp. 1853-1861,
05/01/1990
Copyright © 1990 by The American Society of Hematology
