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Title: Derivatized gold clusters and antibody-gold cluster conjugates

Abstract

Antibody- or antibody fragment-gold cluster conjugates are shown wherein the conjugate size can be as small as 5.0 nm. Methods and reagents are disclosed in which antibodies, Fab' or F(ab')[sub 2] fragments are covalently bound to a stable cluster of gold atoms. The gold clusters may contain 6, 8, 9, 11, 13, 55 or 67 gold atoms in their inner core. The clusters may also contain radioactive gold. The antibody-cluster conjugates are useful in electron microscopy applications as well as in clinical applications that include imaging, diagnosis and therapy. 7 figs.

Inventors:
;
Publication Date:
OSTI Identifier:
6871214
Patent Number(s):
US 5360895; A
Application Number:
PPN: US 7-988338
Assignee:
Associated Universities, Inc., Washington, DC (United States) PTO; EDB-94-170308
DOE Contract Number:
AC02-76CH00016
Resource Type:
Patent
Resource Relation:
Patent File Date: 9 Dec 1992
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 59 BASIC BIOLOGICAL SCIENCES; ANTIBODIES; LABELLING; GOLD ISOTOPES; RADIOIMMUNODETECTION; RADIOIMMUNOTHERAPY; RADIOPHARMACEUTICALS; DIAGNOSTIC TECHNIQUES; DRUGS; IMMUNOTHERAPY; ISOTOPE APPLICATIONS; ISOTOPES; LABELLED COMPOUNDS; MEDICINE; NUCLEAR MEDICINE; RADIOLOGY; RADIOTHERAPY; THERAPY; TRACER TECHNIQUES 550601* -- Medicine-- Unsealed Radionuclides in Diagnostics; 550604 -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-); 550201 -- Biochemistry-- Tracer Techniques

Citation Formats

Hainfeld, J.F., and Furuya, F.R. Derivatized gold clusters and antibody-gold cluster conjugates. United States: N. p., 1994. Web.
Hainfeld, J.F., & Furuya, F.R. Derivatized gold clusters and antibody-gold cluster conjugates. United States.
Hainfeld, J.F., and Furuya, F.R. 1994. "Derivatized gold clusters and antibody-gold cluster conjugates". United States. doi:.
@article{osti_6871214,
title = {Derivatized gold clusters and antibody-gold cluster conjugates},
author = {Hainfeld, J.F. and Furuya, F.R.},
abstractNote = {Antibody- or antibody fragment-gold cluster conjugates are shown wherein the conjugate size can be as small as 5.0 nm. Methods and reagents are disclosed in which antibodies, Fab' or F(ab')[sub 2] fragments are covalently bound to a stable cluster of gold atoms. The gold clusters may contain 6, 8, 9, 11, 13, 55 or 67 gold atoms in their inner core. The clusters may also contain radioactive gold. The antibody-cluster conjugates are useful in electron microscopy applications as well as in clinical applications that include imaging, diagnosis and therapy. 7 figs.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = 1994,
month =
}
  • Antibody- or antibody fragment-gold cluster conjugates are shown wherein the conjugate size can be as small as 5.0 nm. Methods and reagents are disclosed in which antibodies, Fab' or F(ab').sub.2 fragments thereof are covalently bound to a stable cluster of gold atoms. The gold clusters may contain 6, 8, 9, 11, 13, 55 or 67 gold atoms in their inner core. The clusters may also contain radioactive gold. The antibody-cluster conjugates are useful in electron microscopy applications as well as in clinical applications that include imaging, diagnosis and therapy.
  • Antibody- or antibody fragment-gold cluster conjugates are shown wherein the conjugate size can be about 5.0 nm. Methods and reagents are disclosed in which antibodies or Fab' fragments thereof are covalently bound to a stable cluster of gold atoms. 2 figs.
  • A simple method for the synthesis of 1,4,7, 10-tetraazacyclododecane N,N{prime}N{double_prime},N{prime}{double_prime}-tetraacetic acid and 1,4,8,11-tetraazacyclotetradecane N,N{prime},N{double_prime},N{prime}{double_prime}-tetraacetic acid involves cyanomethylating 1,4,7,10-tetraazacyclododecane or 1,4,8,11-tetraazacyclotetradecane to form a tetranitrile and hydrolyzing the tetranitrile. These macrocyclic compounds are functionalized through one of the carboxylates and then conjugated to various biological molecules including monoclonal antibodies. The resulting conjugated molecules are labeled with radiometals for SPECT and PET imaging and for radiotherapy. 4 figs.
  • A simple method for the synthesis of 1,4,7, 10-tetraazacyclododecane N,N'N",N'"-tetraacetic acid and 1,4,8,11-tetraazacyclotetradecane N,N',N",N'"-tetraacetic acid involves cyanomethylating 1,4,7, 10-tetraazacyclododecane or 1,4,8,11-tetraazacyclotetradecane to form a tetranitrile and hydrolyzing the tetranitrile. These macrocyclic compounds are functionalized through one of the carboxylates and then conjugated to various biological molecules including monoclonal antibodies. The resulting conjugated molecules are labeled with radiometals for SPECT and PET imaging and for radiotherapy.
  • Monoclonal antibodies (MAbs) specific for cellobiohydrolase I (CBH I) and endoglucanase I (EG I) were conjugated to 10- and 15-nm colloidal gold particles, respectively. The binding of CBH I and EG I was visualized by utilizing the MAb-colloidal gold probes. The visualization procedure involved immobilization of cellulose microfibrils on copper electron microscopy grids, incubation of the cellulose-coated grids with cellulase(s), binding of MAb-colloidal gold conjugates to cellulase(s), and visualization via transmission electron microscopy. CBH I was seen bound to apparent crystalline cellulose as well as apparent amorphous cellulose. EG I was seen bound extensively to apparent amorphous cellulose with minimalmore » binding to crystalline cellulose.« less