A new bifunctional chelate, BrMe sub 2 HBED: An effective conjugate for radiometals and antibodies

Journal Article · Wed Apr 18 04:00:00 EDT 1990 · Inorganic Chemistry; (USA)

DOI:https://doi.org/10.1021/ic00333a007· OSTI ID:6873222

Mathias, C J; Connett, J M; Philpott, G W; Welch, M J ^[1]; Sun, Yizhen; Martell, A E ^[2]

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1. Washington Univ. School of Medicine, St. Louis, MO (USA)
2. Texas A and M Univ., College Station (USA)

A new bifunctional chelate, N-(2-hydroxy-3,5-dimethylbenzyl)-N{prime}-(2-hydroxy-5-(bromoacetamido)benzyl)ethylenediamine-N,-N{prime}-diacetic acid (BrMe{sub 2}HBED), was designed and synthesized to bind trivalent cationic metals with monoclonal antibodies. The stability constants (log values) for indium complexed with a similar ligand, HBED, were increased over those of more commonly used ligands DTPA and EDTA. Predictably, the increased metal-ligand complex stability would expedite the in vivo clearance from nontarget regions and perhaps enhance the localization of the radiolabeled antibody (Ab). BrMe{sub 2}HBED was conjugated with the Ab (24 h) and then radiolabeled with indium-111 citrate (24 h). Additionally, the Ab was radiolabeled by using conventional methods ({sup 111}In-DTPA and {sup 125}I-lactoperoxidase) and then compared by measuring the in vitro stability, in vitro immunoreactivity(IR), and in vivo distribution and clearance. A 10:1 BrMe{sub 2} HBED:Ab mole ratio resulted in good labeling efficiency with {sup 111}In and more importantly a very high IR. In a hamster tumor model, {sup 111}In-BrMe{sub 2} HBED-labeled monoclonal antibody (1A3) had high uptake in the tumor tissue and preferable blood clearance compared to either of the more conventional radiolabeled 1A3 monoclonal antibodies ({sup 111}In-DTPA or {sup 125}I-lactoperoxidase). 49 refs., 4 figs., 8 tabs.

• DOE Contract Number: FG02-87ER60512
• OSTI ID: 6873222
• Journal Information: Inorganic Chemistry; (USA), Journal Name: Inorganic Chemistry; (USA) Vol. 29:8; ISSN 0020-1669; ISSN INOCA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
CHELATING AGENTS
CHEMICAL PREPARATION
DATA
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
EXPERIMENTAL DATA
GADOLINIUM 153
GADOLINIUM ISOTOPES
GALLIUM 68
GALLIUM ISOTOPES
HOURS LIVING RADIOISOTOPES
HYDROXY COMPOUNDS
IMMUNOLOGY
IMMUNOTHERAPY
INDIUM 111
INDIUM ISOTOPES
INFORMATION
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MEDICINE
MINUTES LIVING RADIOISOTOPES
MONOCLONAL ANTIBODIES
NUCLEAR MEDICINE
NUCLEI
NUMERICAL DATA
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC BROMINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOISOTOPES
RADIOLOGY
RADIOPHARMACEUTICALS
RADIOTHERAPY
RARE EARTH ISOTOPES
RARE EARTH NUCLEI
SYNTHESIS
THERAPY