title: Efficient bifunctional decadentate ligand 3p-C-DEPA for targeted α-radioimmunotherapy applications.
abstract: A new bifunctional ligand 3p-C-DEPA was synthesized and evaluated for use in targeted α-radioimmunotherapy. 3p-C-DEPA was efficiently prepared via regiospecific ring opening of an aziridinium ion and conjugated with trastuzumab. The 3p-C-DEPA-trastuzumab conjugate was extremely rapid in binding (205/6)Bi, and the corresponding (205/6)Bi-3p-C-DEPA-trastuzumab complex was stable in human serum. Biodistribution studies were performed to evaluate in vivo stability and tumor targeting of (205/6)Bi-3p-C-DEPA-trastuzumab conjugate in tumor bearing athymic mice. (205/6)Bi-3p-C-DEPA-trastuzumab conjugate displayed excellent in vivo stability and targeting as evidenced by low organ uptake and high tumor uptake. The results of the in vitro and in vivo studies indicate that 3p-C-DEPA is a promising chelator for radioimmunotherapy of (212)Bi and (213)Bi.
authors: Chemistry Division, Biological, Chemical, and Physical Sciences Department, Illinois Institute of Technology, Chicago, Illinois, United States.
authors: Hyun A
authors: HA
authors: Song
authors: Chi Soo
authors: CS
authors: Kang
authors: Kwamena E
authors: KE
authors: Baidoo
authors: Diane E
authors: DE
authors: Milenic
authors: Yunwei
authors: Y
authors: Chen
authors: Anzhi
authors: A
authors: Dai
authors: M W
authors: MW
authors: Brechbiel
authors: Hyun-Soon
authors: HS
authors: Chong
references: Nucl Med Biol. 2003 Aug;30(6):581-95
references: 12900284
references: Appl Radiat Isot. 2002 Dec;57(6):841-7
references: 12406626
references: Chem Commun (Camb). 2011 May 21;47(19):5584-6
references: 21468393
references: Semin Radiat Oncol. 2000 Apr;10(2):73-93
references: 10727597
references: Cancer Biol Ther. 2005 Dec;4(12):1318-24
references: 16322682
references: Nat Rev Drug Discov. 2004 Jun;3(6):488-99
references: 15173838
references: Cancer Biother Radiopharm. 2005 Oct;20(5):557-68
references: 16248771
references: Int J Radiat Oncol Biol Phys. 1996 Feb 1;34(3):609-16
references: 8621285
references: Blood. 2002 Aug 15;100(4):1233-9
references: 12149203
references: J Biol Chem. 1951 Nov;193(1):265-75
references: 14907713
references: Clin Cancer Res. 2004 Dec 1;10(23):7834-41
references: 15585615
references: Clin Cancer Res. 2006 Jun 15;12(12):3843-50
references: 16778112
references: Semin Oncol. 2000 Dec;27(6 Suppl 11):53-63; discussion 92-100
references: 11236029
references: Clin Cancer Res. 2008 Jun 1;14(11):3555-61
references: 18519789
references: Ann Oncol. 2001;12 Suppl 1:S49-55
references: 11521722
references: Nucl Med Biol. 2004 Aug;31(6):795-802
references: 15246371
references: J Nucl Med. 1999 Jan;40(1):166-76
references: 9935073
references: Cancer Biother Radiopharm. 2001 Apr;16(2):133-46
references: 11385960
references: Clin Cancer Res. 2005 Aug 1;11(15):5616-21
references: 16061880
references: Chem Rev. 2001 Jul;101(7):2019-36
references: 11710239
references: Bioorg Med Chem Lett. 2008 Nov 1;18(21):5792-5
references: 18845437
references: Int J Rad Appl Instrum A. 1988;39(4):283-6
references: 2838433
references: Clin Cancer Res. 2004 Jul 1;10(13):4489-97
references: 15240541