当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Evaluation of the stability and animal biodistribution of gadolinium (III) benzylamine-derivatized diethylenetriaminepentaacetic acid.

Evaluation of the stability and animal biodistribution of gadolinium (III) benzylamine-derivatized diethylenetriaminepentaacetic acid.

Abstract：

:The need for a readily available Gd(III) bifunctional chelate for protein conjugation has led to the development of LDTPA (N,N-bis[2-[N',N'-bis(carboxymethyl)amino]- ethyl]-4-amino-L-phenyl-alanine). The benzylamine group is readily converted to the isothiocyanato group (SCN-LDTPA) by treatment of the lithium salt of LDTPA with thiophosgene. SCN-LDTPA was successfully conjugated to three proteins, BSA (bovine serum albumin), mannose BSA, and galactose BSA. All protein conjugates were labeled with 111In3+ or 153Gd3+. Competition of Gd-LDTPA with DTPA (diethylenetriaminepentaacetic acid) resulted in a log stability constant of 21.2. The thermodynamic stability constant of Gd-LDTPA was also measured. The log Gd(III) stability constant (log K) is 21.99, and the log protonation constants (pKa's) are 10.16, 8.92, 5.35, 3.93, 2.71, and 1.89. Comparison of the thermodynamic stability constants for Gd(LDTPA)2- with other DTPA derivatives indicates that the stability of Gd(LDTPA)2- is similar to Gd(DTPA)2- (log K = 22.4), and higher than DTPA derivatives with one or more carboxylate arm(s) functionalized. The biodistribution of 153Gd-LDTPA-protein conjugates is consistent with the in vitro stability measurements. By monitoring the bone accumulation of 153Gd3+, 153Gd-LDTPA-protein shows a higher in vivo stability than 153Gd-DTPA-protein, the radiolabeled protein conjugate formed by the reaction of DTPA dianhydride with proteins.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Deal KA,Motekaitis RJ,Martell AE,Welch MJ

doi

10.1021/jm9602118

subject

Has Abstract

pub_date

1996-08-02 00:00:00

pages

3096-3106

issue

16

eissn

0022-2623

issn

1520-4804

pii

jm9602118

journal_volume

39

pub_type

杂志文章

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