99mTc-monoclonal antibody radiolabeled via hydrazino nicotinamide derivative for imaging disialoganglioside G(D2)-positive tumors.
3F8 is a murine IgG3 monoclonal antibody (MAb) selective for the ganglioside G(D2). Previous studies using 131I-3F8 have shown great potential in the imaging of neuroectodermal tumors and the therapy of human neuroblastoma. 131I is commonly used in radioimmunodiagnosis, but its relatively long half-life (8 days) and its high energy gamma-emission (364 KeV) are suboptimal for imaging purposes when compared with 99mTc (6 h and 140 KeV, respectively). To label 3F8 with 99mTc, the antibody was first coupled with a heterobifunctional linker, succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH), obtaining a hydrazinonicotinamide-antibody conjugate. Using 99mTc-Tricine as the precursor complex, 3F8-SHNH was coupled efficiently to 99mTc, resulting in >90% radiometal incorporation, with a specific activity >10 mCi/mg and retaining full immunoreactivity. Immunoscintigraphy at 6, 22, and 46 h after intravenous injection of 1 mCi of 99mTc-3F8 showed selective neuroblastoma localization in xenografted nude mice, comparable to that obtained with the injection of 100 microCi of 131I-3F8. Biodistribution studies of 131I-3F8 and 99mTc-3F8 in mice demonstrated comparable %ID/g uptake in tumor (with a T/B ratio: approximately 2.5 at 24 h and approximately 3.5 at 48 h) and normal organs, including blood, except for spleen and liver which had about a three times higher uptake of the 99mTc conjugate. In conclusion, 99mTc can be coupled conveniently at high specific activity to 3F8 without compromising immunoreactivity. SHNH appears to be a useful linker for 99mTc in tumor diagnostic imaging and may have potential utility in coupling other radioisotopes (e.g., 94mTc) for positron imaging and therapy.
Fonti
R
R
Department of Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cheung
N K
NK
Bridger
G J
GJ
Guo
H F
HF
Abrams
M J
MJ
Larson
S M
SM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D005732:Gangliosides / Q000032:analysis*; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000000981:diagnostic imaging*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000737:chemistry; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013388:Succinimides / Q000737:chemistry; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D007457:Iodine Radioisotopes; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D013388:Succinimides; C073102:succinimidyl 6-hydrazinonicotinate; D009536:Niacinamide; C019403:ganglioside, GD2