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

Journal Article · Tue May 01 04:00:00 EDT 1990 · Blood (Journal of Hematology); (USA)

OSTI ID:6774098

Faguet, G B; Agee, J F; DiPiro, J T ^[1]

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1. Veterans Administration Medical Center, Augusta, GA (USA)

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.

• OSTI ID: 6774098
• Journal Information: Blood (Journal of Hematology); (USA), Journal Name: Blood (Journal of Hematology); (USA) Vol. 75:9; ISSN BLOOA; ISSN 0006-4971
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
ANTIBODIES
ANTIGENS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MARKERS
BLOOD-PLASMA CLEARANCE
CLEARANCE
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DIAGNOSIS
DIAGNOSTIC TECHNIQUES
DISEASES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
EXPERIMENTAL NEOPLASMS
HEMIC DISEASES
IMMUNE SYSTEM DISEASES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE 131
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LEUKEMIA
MAMMALS
MAN
MICE
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
PRIMATES
RADIOIMMUNODETECTION
RADIOIMMUNOSCINTIGRAPHY
RADIOISOTOPE SCANNING
RADIOISOTOPES
RODENTS
SCINTISCANNING
SPECIFICITY
TISSUE DISTRIBUTION
TRACER TECHNIQUES
VERTEBRATES