New bifunctional ligands for radioimmunoimaging and radioimmunotherapy
The bifunctional EDTA ligand and two bifunctional DTPA ligands were synthesized by direct aminolysis of an amino acid ester followed by reduction, alkylation, and functional group modification to introduced bifunctionality. The reactive substituent chosen for protein conjugation was the isothiocyanate group. The generality of this approach was demonstrated with 9 different amino acids to produce the respective substituted diethylenetriamines. The remaining three bifunctional DTPA ligands were synthesized via classical peptide methodology producing a dipeptide amide which, after deprotection, was reduced to the triamine and alkylated to produce the ligand. Biodistribution studies of the ligands conjugated to monoclonal antibody B72.3 and labelled with In-111 revealed that superior retention of In-111 was attained and the dose to the liver was minimized when a full intact octadentate bifunctional DTPA chelate was used, e.g. DTPA > EDTA > DTTA (diethylenetritetraacetic acid from use of DTPA dianhydride (CA-DTPA)). The best scintigraphic images were obtained after 72 hours when a DTPA ligand was used to complex the In-111. Biodistribution studies using Yttrium-88 revealed that the disubstituted bifunctional DTPA was necessary to minimize the bone dose from the Yttrium while maintaining a high dose to the tumor.
- Research Organization:
- American Univ., Washington, DC (USA)
- OSTI ID:
- 6485193
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550604 -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACIDS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CHELATING AGENTS
CHEMICAL PREPARATION
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DRUGS
DTPA
EDTA
ELECTRON CAPTURE RADIOISOTOPES
IMMUNOLOGY
IMMUNOTHERAPY
INDIUM 111
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGANDS
MEDICINE
MINUTES LIVING RADIOISOTOPES
MONOCLONAL ANTIBODIES
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
RADIOIMMUNODETECTION
RADIOIMMUNOLOGY
RADIOIMMUNOSCINTIGRAPHY
RADIOIMMUNOTHERAPY
RADIOISOTOPE SCANNING
RADIOISOTOPES
RADIOLOGY
RADIOPHARMACEUTICALS
RADIOPROTECTIVE SUBSTANCES
RADIOTHERAPY
SCINTISCANNING
SECONDS LIVING RADIOISOTOPES
SYNTHESIS
THERAPY
TISSUE DISTRIBUTION
TRACER TECHNIQUES
YTTRIUM 88
YTTRIUM ISOTOPES