Labeling of monoclonal antibodies with samarium-153 for combined radioimmunoscintigraphy and radioimmunotherapy.
The labeling of a monoclonal antibody K-1-21 with 153Sm has been investigated using the bifunctional chelate cyclic diethylenetriaminepentaacetic acid (DTPA) anhydride. Labeling efficiencies greater than 60% were obtained using high specific activity [153Sm]chloride and a cDTPAa:MAb conjugation ratio of 20:1. The resultant labeled antibody had a s.a. greater than 150 MBq.mg-1 and a % retained immunoreactivity greater than 90%. Imaging and biodistribution studies in a rat model demonstrated that specific uptake of 153Sm-K-1-21 into s.c. implants of the target antigen could be clearly detected in scintigrams at 6 days p.i. The specific uptake (1.90 +/- 0.45% ID/g, 19.95 +/- 2.20 Implant:Blood ratio) compared favorably to 131I- and 111In-labeled K-1-21 (2.52 +/- 0.20 and 3.33 +/- 0.20% ID/g, 7.69 +/- 0.45 and 10.10 +/- 0.60 I:B, respectively). Labeling of MAbs with 153Sm for combined scintigraphy/therapy is feasible at clinically appropriate specific activities using cDTPAa, with the resultant conjugates retaining immunoreactivity and in vivo antigen localization.
Boniface
G R
GR
Australian Nuclear Science and Technology Organisation, University of Sydney, NSW.
Izard
M E
ME
Walker
K Z
KZ
McKay
D R
DR
Sorby
P J
PJ
Turner
J H
JH
Morris
J G
JG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000378:metabolism / Q000627:therapeutic use; D000922:Immunotoxins / Q000378:metabolism / Q000627:therapeutic use; D007205:Indium Radioisotopes / Q000378:metabolism / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D004369:Pentetic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use; D011868:Radioisotopes / Q000378:metabolism / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D012493:Samarium / Q000378:metabolism / Q000627:therapeutic use; D013997:Time Factors; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D000922:Immunotoxins; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D011868:Radioisotopes; D012493:Samarium; D004369:Pentetic Acid