Investigation into the Use of a Diaminodihydroxyaryl Derivative of Ethylenediaminetetraacetic Acid (DAHA-EDTA) for Cu-64 PET Imaging and Radioimmunotherapy
| Autor: | Martalena Ramli, Nadine Di Bartolo, Peter Frederick Schmidt, Suzanne V. Smith |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
chemistry.chemical_classification
Biodistribution biology 010405 organic chemistry Ligand Stereochemistry medicine.medical_treatment Peptide Ethylenediaminetetraacetic acid General Chemistry biology.organism_classification 01 natural sciences 0104 chemical sciences Amino acid 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Nude mouse chemistry 030220 oncology & carcinogenesis Radioimmunotherapy medicine Carbodiimide Nuclear chemistry |
| Zdroj: | Australian Journal of Chemistry. 70:614 |
| ISSN: | 0004-9425 |
| DOI: | 10.1071/ch16647 |
| Popis: | A diaminodihydroxyaryl derivative of ethylenediaminetetraacetic acid (DAHA-EDTA) was synthesised in two steps and evaluated for Cu-64 radiolabelling of the B72.3 antibody. The ligand complexes Cu-64 rapidly in a pH range 4 to 7. The Cu-64 complex of the parent species N,N′-bis(carboxymethyl)-N,N′-bis(2-hydroxyacetanilido)-1,2-diaminoethane (DHA-EDTA) shows good stability in serum at 37°C for up to 72 h. Conjugation of the Cu-64-DAHA-EDTA to the B72.3 antibody was achieved using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as the activating agent. The reaction conditions were optimized for protein concentration and molar ratio of Cu-64-DAHA-EDTA and EDC to antibody. The specific activity of the final [Cu-64-DAHA-EDTA]-B72.3 product was 49 MBq mg−1 at the end of synthesis. The biodistribution of [Cu-64-DAHA-EDTA]-B72.3 in LS174t tumour-bearing nude mice was monitored over a 24 h period. Maximum tumour uptake (25.8 ± 7.5 % ID g−1) was achieved at 16 h and maintained at 24 h (21.6 ± 1.8 % ID g−1). Rapid clearance of the [Cu-64-DAHA-EDTA]-B72.3 from the blood resulted in good tumour-to-blood ratios (≈ 3.3) within a shorter period (6 h) than previously reported with B72.3 whole antibody and the LS174t tumour bearing nude mouse model. |
| Databáze: | OpenAIRE |
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