Investigation into the Use of a Diaminodihydroxyaryl Derivative of Ethylenediaminetetraacetic Acid (DAHA-EDTA) for Cu-64 PET Imaging and Radioimmunotherapy
Martalena Ramli A B C , Peter F. Schmidt B D , Nadine Di Bartolo B and Suzanne V. Smith B E FA Centre for Radioisotope and Radiopharmaceutical Technology, National Nuclear Energy Agency, B. 11, Kawasan PUSPIPTEK, Serpong–Tangerang Selatan 15314, Banten, Indonesia.
B Australian Nuclear Science and Technology Organization, Locked Bag 2001, Kirrawee DC, Sydney, NSW 2232, Australia.
C School of Chemistry, F11, University of Sydney, Sydney, NSW 2006, Australia.
D Q Biotics, Suite 3A, Level 1, Taringa Central, 165 Moggill Road, Taringa, Qld 4068, Australia.
E Idaho Accelerator Centre, Idaho State University, 1500 Alvin Ricken Drive, Pocatello, ID 83201, USA.
F Corresponding author. Email: Suzanneoznq@gmail.com
Australian Journal of Chemistry 70(5) 614-622 https://doi.org/10.1071/CH16647
Submitted: 15 November 2016 Accepted: 23 February 2017 Published: 10 April 2017
Abstract
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.
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