(99m)Tc-monoclonal antibody radiolabeled via hydrazino nicotinamide derivative for imaging disialoganglioside G(D2)-positive tumors Journal Article
| Authors: | Fonti, R.; Cheung, N. K. V.; Bridger, G. J.; Guo, H. F.; Abrams, M. J.; Larson, S. M. |
| Article Title: | (99m)Tc-monoclonal antibody radiolabeled via hydrazino nicotinamide derivative for imaging disialoganglioside G(D2)-positive tumors |
| Abstract: | 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. |
| Keywords: | controlled study; unclassified drug; human cell; comparative study; technetium 99m; radiopharmaceuticals; mouse; animal; animals; mice; tumor cells, cultured; monoclonal antibody; antibodies, monoclonal; chemistry; diagnostic agent; radioactive iodine; drug distribution; isotope labeling; xenograft; cell culture; nude mouse; tissue distribution; iodine radioisotopes; mice, nude; neuroblastoma; ganglioside gd2; neuroblastoma cell; radiopharmaceutical agent; drug derivative; scintiscanning; transplantation, heterologous; imaging; high performance liquid chromatography; immunoglobulin g3; tumor; organotechnetium compounds; biodistribution; gangliosides; ganglioside; 3f8; nicotinamide; ganglioside, gd2; immunoscintigraphy; succinimide derivative; succinimides; niacinamide; technetium complex; humans; human; article; 99mtc-labeling; shnh; succinylimidyl 6 hydrazinonicotinate; succinimidyl 6 hydrazinonicotinate; succinimidyl 6-hydrazinonicotinate |
| Journal Title: | Nuclear Medicine and Biology |
| Volume: | 26 |
| Issue: | 6 |
| ISSN: | 0969-8051 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 1999-08-01 |
| Start Page: | 681 |
| End Page: | 686 |
| Language: | English |
| DOI: | 10.1016/s0969-8051(99)00026-8 |
| PUBMED: | 10587107 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work