Reference

Radioimmunotherapy of A431 xenografted mice with pretargeted B3 antibody-streptavidin and 90Y-labeled 1,4,7,10-Tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA)-biotin

Radioimmunotherapy of A431 xenografted mice with pretargeted B3 antibody-streptavidin and 90Y-labeled 1,4,7,10-Tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA)-biotin. Yao, Zhengsheng; Zhang, Meili; Axworthy, Donald B.; Wong, Karen J.; Garmestani, Kayhan; Park, Luke; Park, Chang W.; Mallett, Robert W.; Theodore, Louis J.; Yau, Eric K.; Waldmann, Thomas A.; Brechbiel, Martin W.; Paik, Chang H.; Pastan, Ira; Carrasquillo, Jorge A. (Nuclear Medicine Department of the Warren G. Magnuson Clinical Center, National Cancer Institute, Bethesda, MD 20892, USA). Cancer Research, 62(20), 5755-5760 (English) 2002 American Association for Cancer Research. CODEN: CNREA8. ISSN: 0008-5472. DOCUMENT TYPE: Journal CA Section: 8 (Radiation Biochemistry) We investigated the biodistribution of 88Y/111In-labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA)-biotin and therapy with 90Y-labeled DOTA-biotin in tumor-bearing mice after B3-streptavidin antibody conjugate (B3-SA) pretargeting. B3 antibody, recognizing Lewisy antigen, was conjugated to streptavidin (B3-SA). For pretargeting, 400 mg of the B3-SA was injected i.v. into mice bearing A431 tumor xenografts. After tumor localization of B3-SA, 100 mg of synthetic clearing agent was injected i.v. to clear the unbound B3-SA from the circulation. Four h later, 1 mg of radiolabeled DOTA-biotin was injected i.v. Radioimmunotherapy was performed with doses of 9.25 to 37 MBq of 90Y-labeled DOTA-biotin. As a result, radiolabeled DOTA-biotin cleared rapidly. All of the normal tissues had <2.6% of the injected dose per g, whereas tumor uptake reached ~15% ID/g. The total tumor uptake of radioactivity remained similar for 96 h or longer. In the first study, the median survival of the control group was 8 days, whereas it increased to >163 days in the 37 MBq 90Y group (P < 0.005). In a second therapy group, 7 of 10 mice receiving 37 MBq of 90Y and B3-SA were cured, and remained healthy for >180 days after therapy, compared with control groups, with ￡29.2 days mean survival time (P < 0.001). Tumor pretargeting with B3-SA and radiolabeled DOTA-biotin has shown favorable, specific, and fast targeting that has resulted in good tumor responses and, thus, serves as a rationale for human studies with the B3-SA pretargeting approach.

NMR Studies of the Lanthanide(III) Complexes of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetrakis(methanephosphoni c acid mono(2',2',2-trifluoroethyl) ester)

NMR Studies of the Lanthanide(III) Complexes of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetrakis(methanephosphoni c acid mono(2',2',2-trifluoroethyl) ester). Kim, Won D.; Kiefer, Garry E.; Huskens, Jurriaan; Sherry, A. Dean ( Department of Chemistry, University of Texas at Dallas, Richardson, TX 75083-0688, USA). Inorganic Chemistry, 36(18), 4128-4134 (English) 1997 American Chemical Society. CODEN: INOCAJ. ISSN: 0020-1669. DOCUMENT TYPE: Journal CA Section: 68 (Phase Equilibriums, Chemical Equilibriums, and Solutions) Section cross-reference(s): 77 A new macrocyclic ligand 1,4,7,10,-tetraazacyclododecane-1,4,7,10-tetrakis(methanephosphonic acid mono(2',2',2'-trifluoroethyl) ester) (F-DOTPME) was prepd. and some of its metal binding properties examd. The ligand protonation consts. (log K1 = 10.5, log K2 = 6.7) and its stability const. with CaII (log KCaL = 8.4) were detd. by pH potentiometry. The stability of the LaIII complex could not be detd. by potentiometry so it was evaluated in an EDTA competition expt. by using 31P NMR to monitor the reaction. The dissocn. kinetics of La(F-DOTPME)- was slow, with a kd,obs of only 1.0 ′ 10-7 s-1. A series of Ln(F-DOTPME)- complexes (LnIII = La, Gd, Dy, Tm, and Yb) were examd. by multinuclear NMR. The spectra show that these complexes exist in aq. soln. as a mixt. of stereoisomers of nearly equal energy (energy differences of less than 1 kJ/mol). Several resolved 19F resonances in the NMR spectra of the Dy(F-DOTPME)-, Tm(F-DOTPME)-, and Yb(F-DOTPME)- complexes have been assigned to specific diastereomers by comparing resonance integrals, assuming an interaction model between neighboring pendant arms, and the magnitude and direction of the hyperfine 19F NMR shifts induced by the paramagnetic lanthanide cation. Cationic detergents added to two different Ln(F-DOTPME)- complexes altered the distribution of isomers in favor of the sym. D-SSSS isomer, while neutral polyethylene glycol affected the 19F chem. shifts of some isomers without altering their populations. Gd(F-DOTPME)- displayed a water proton relaxivity (R1) of 2.5 mM-1 s-1 at 25° and 40 MHz, typical of complexes lacking an inner-sphere-coordinated water mol. 17O NMR was used to confirm that Dy(F-DOTPME)- does not have an inner-sphere-coordinated water mol. Addn. of human serum albumin to aq. solns. of Gd(F-DOTPME)- produced a 4-fold increase in water relaxivity, and an anal. of binding curves indicated the fluorinated complex binds to HSA with a binding const. of about 0.17 mM.