Affiliations: Depts. of Dept. of Nuclear Medicine, Mem. Sloan-Kettering Cancer Center, New York, NY, United States
Department of Pediatrics, Mem. Sloan-Kettering Cancer Center, New York, NY, United States
AnorMed Inc., Langley, BC, Canada
References: Not available.
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 γ-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 μCi 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: ~2.5 at 24 h and ~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. Copyright (C) 1999 Elsevier Science Inc.
99mTc-monoclonal antibody radiolabeled via hydrazino nicotinamide derivative for imaging disialoganglioside G(D2)-positive tumors