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.
References
[1] J. Park, J. Y. Kim, Curr. Top. Med. Chem. 2013, 13, 458.| CrossRef | 1:CAS:528:DC%2BC3sXovFektrs%3D&md5=a7564494af35cdd14bd45dcf0aa4f592CAS |
[2] (a) Nuclear Science Advisory Committee (NSAC), The 2015 Long Range Plan For the DOE-NP Isotope Program. Available at: http://science.energy.gov/~/media/np/nsac/pdf/docs/2015/2015_NSACI_Report_to_NSAC_Final.pdf
(b) A. N. Asabella, G. L. Cascini, C. Altini, D. Paparella, A. Notaristefano, G. Rubini, BioMed Res. Int. 2014, 2014, 786463.
| CrossRef |
(c) S. V. Smith, Expert Opin. Drug Discovery 2007, 2, 659.
| CrossRef |
(d) S. V. Smith, J. Inorg. Biochem. 2004, 98, 1874.
| CrossRef |
[3] N. Di Bartolo, S. V. Smith, E. Hetherington, A. M. Sargeson, Aust. J. Chem. 2009, 62, 1261.
| CrossRef | 1:CAS:528:DC%2BD1MXht1Kis77E&md5=538837492f94ace277a5e3217a0909c5CAS |
[4] (a) M. N. Naomm, K. H. Ahmed, N. F. Naji, Int. J. Phys. Res. 2013, 3, 13.
(b) F. Szelecsényi, Z. Kovács, K. Nagatsu, M. Znhang, K. Suzuki, Radiochim. Acta 2014, 102, 465.
| CrossRef |
[5] (a) N. I. Ayzatskiy, N. P. Dikiy, A. N. Dovbnya, Yu. V. Lyashko, V. I. Nikiforov, B. I. Shramenko, A. Eh. Tenishev, A. V. Torgovkin, V. L. Uvarov, in Cyclotrons and their Applications: 18th International Conference 2007, 243–245.
(b) N. A. Smith, D. L. Bowers, D. A. Ehst, Appl. Radiat. Isot. 2012, 70, 2377.
| CrossRef |
[6] (a) V. I. Nikiforov, V. L. Uvarov, Nucl. Instrum. Methods Phys. Res. B 2011, 269, 3149.
| CrossRef | 1:CAS:528:DC%2BC3MXhsV2htrfO&md5=393697553ce054f130abaa584a7f948bCAS |
(b) S. Howard, V. N. Starovoitova, Appl. Radiat. Isot. 2015, 96, 162.
| CrossRef |
(c) V. N. Starovoitova, P. L. Cole, T. L. Grimm, J. Radioanal. Nucl. Chem. 2015, 305, 127.
| CrossRef |
[7] (a) C. J. Anderson, R. Ferdani, Cancer Biother. Radiopharm. 2009, 24, 379.
| CrossRef | 1:CAS:528:DC%2BD1MXhtVGjurfJ&md5=ef443f6d1c25348a2a5d1cc6581bc4cfCAS |
(b) Z. Cai, C. J. Anderson, J. Labelled Comp. Radiopharm. 2014, 57, 224.
| CrossRef |
[8] A. Thor, N. Ohuchi, C. A. Szpak, W. W. Johnston, J. Schlom, Cancer Res. 1986, 46, 3228.
[9] (a) R. T. Maguire, R. F. R. Schmelter, V. L. Pascucci, J. J. Conklin, Antibody, Immunoconjugates, Radiopharm. 1998, 2, 257.
(b) D. E. Milenic, M. Roselli, M. W. Brechbiel, C. G. Pippin, T. J. McMurray, J. O. Carrasquillo, D. Colcher, R. Lambrecht, O. Gansow, J. Schlom, Nucl. Med. 1998, 25, 471.
(c) S. M. Larson, J. A. Carrasqillo, D. C. Colcher, K. Yokoyoma, J. C. Reynols, A. Bacharach, A. Raubitcheck, L. Pace, R. D. Finn, M. Rotman, M. Stabin, R. D. Neuman, P. Sugarbaker, J. Schlom, J. Nucl. Med. 1992, 32, 1661.
(d) D. Colcher, M. F. Minelli, M. Roselli, R. Muraro, J. Schlom, Cancer Res. 1988, 48, 4597.
(e) D. Colcher, A. M. Keenan, M. S. Larson, R. Schlom, Cancer Res. 1984, 44, 5744.
(f) B. A. Brown, C. B. Deaborn, C. A. Drozynski, H. Sands, Cancer Res. 1990, 50, 835s.
(g) K. D. Brandt, D. K. Johnson, Bioconjug. Chem. 1992, 3, 118.
| CrossRef |
(h) M. Roselli, J. Schlom, O. A. Gansow, M. W. Brechbiel, S. Mirzadeh, C. G. Pippin, D. E. Milenic, D. Colcher, Nucl. Med. Biol. 1990, 18, 389.
(i) W. B. Webster, S. J. Harwood, R. G. Caroll, M. A. Morrissey, J. Nucl. Med. 1992, 33, 498.
(j) H. S. Rosenzweig, G. N. Ranadive, T. Seskey, M. W. Epperly, W. D. Bloomer, Nucl. Med. Biol. 1994, 21, 171.
| CrossRef |
[10] N. Di Bartolo, A. M. Sargeson, S. V. Smith, Org. Biomol. Chem. 2006, 4, 3350.
| CrossRef | 1:CAS:528:DC%2BD28Xotl2nsbk%3D&md5=d6b4e23cc0b647873d42471f19fee580CAS |
[11] P. F. Schmidt, Radiolabelling of Antibodies for Use in Diagnosis or Treatment of Disease 1997, Ph.D. thesis, University of Sydney.
[12] (a) S. V. Smith, R. M. Lambrecht, P. F. Schmidt, F. T. Lee, T. M. Donlevy, N. M. Di Bartolo, U.S. Patent 5807535 A 1998.
(b) S. V. Smith, R. M. Lambrecht, P. F. Schmidt, F. T. Lee, Patent EP 590766A3 1994.
[13] Oak Ridge Institute for Science and Education, PO Box 117, Oak Ridge, TN 37831, USA.
[14] (a) C. F. Meares, M. K. Moil, H. Diril, D. L. Kukis, M. J. McCall, S. V. Deshpande, S. J. DeNardo, D. Snook, A. A. Epenetos, Br. J. Cancer 1990, 62, 21.
| 1:CAS:528:DyaK3MXislOg&md5=42e8218dbc3599040a454804636b2550CAS |
(b) M. K. Moi, S. J. DeNardo, C. F. Meares, Cancer Res. 1990, 50, 789s.
[15] M. C. Linder, M. Hazegh-Azam, Am. J. Clin. Nutr. 1996, 63, 797s.
| 1:CAS:528:DyaK28XjtVyltL8%3D&md5=3bda527ff1948704bb696ec7c171056fCAS |
[16] (a) D. A. Weber, K. F. Eckerman, L. T. Dillman, J. C. Ryman, MIRD: Radionuclide Data and Decay Schemes 1989 (The Society of Nuclear Medicine, Inc.: Reston, VA).
(b) M. G. Stabin, J. Nucl. Med. 1996, 37, 538.