In vivo evaluation of a lead-labeled monoclonal antibody using the DOTA ligand.
The aim of this study was to assess the utility of a radioimmunoconjugate containing a lead radionuclide for therapy and scintigraphy applications. The radioimmunoconjugate evaluated consisted of a bifunctional DOTA ligand and monoclonal antibody (MAb) B72.3 using athymic mice bearing LS-174T tumors, human colon carcinoma xenografts. In the studies reported here, the lead-203-DOTA complex itself was first demonstrated to have in vivo stability. MAb B72.3 was then conjugated with the DOTA ligand and labeled with 203Pb, and the immunoreactivity of B72.3 was maintained. The localization of the radioimmunoconjugate to tumor tissue and other select organs paralleled that of DOTA-125I-B72.3, suggesting a similar metabolic pattern of the two radioimmunoconjugates. Thus, the DOTA-metal complex does not alter the behavior of the radioimmunoconjugate. Tumor localization of the 203Pb-DOTA-B72.3 conjugate was demonstrated with biodistribution studies as well as immunoscintigraphy studies. Such data highlight the stability of a lead radionuclide in the DOTA ligand. The suitability of this chelation chemistry for labeling radioimmunoconjugates with a lead radionuclide now makes its application in nuclear medicine a feasible proposition.
Milenic
D E
DE
Laboratory of Tumor Immunology and Biology, National Cancer Institute, The National Institutes of Health, Bethesda, MD 20892, USA.
Roselli
M
M
Brechbiel
M W
MW
Pippin
C G
CG
McMurray
T J
TJ
Carrasquillo
J A
JA
Colcher
D
D
Lambrecht
R
R
Gansow
O A
OA
Schlom
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D006571:Heterocyclic Compounds / Q000627:therapeutic use; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007856:Lead Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D006571:Heterocyclic Compounds; D018796:Immunoconjugates; D007856:Lead Radioisotopes; C113007:lead-203 DOTA-B72.3