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A systematic comparative evaluation of 90 Y‐labeled bifunctional chelators for their use in targeted therapy
Author(s) -
Chakravarty Rubel,
Chakraborty Sudipta,
Dash Ashutosh
Publication year - 2014
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3140
Subject(s) - chemistry , bifunctional , in vivo , clearance , chelation , in vitro , dota , combinatorial chemistry , stereochemistry , radiochemistry , pharmacology , nuclear chemistry , biochemistry , organic chemistry , urology , medicine , microbiology and biotechnology , biology , catalysis
This paper describes a systematic comparative evaluation of five commonly used bifunctional chelators, namely, p ‐isothiocyanato benzyl derivatives of diethylenetriaminepentacetic acid (DTPA‐NCS), trans‐cyclohexyl diethylenetriaminepentacetic acid (CHX‐A″‐DTPA‐NCS), 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA‐NCS), 1,4,7‐triazacyclononane‐1,4,7‐triacetic acid (NOTA‐NCS), and 3,6,9,15‐tetraazabicyclo [9.3.1]pentadeca‐1(15),11,13‐triene‐3,6,9‐triacetic acid (PCTA‐NCS), on the basis of their ability to complex 90 Y at room temperature, in vitro and in vivo stability and clearance pattern in biological system. The results of the experiments carried out revealed that CHX‐A″‐DTPA‐NCS was the most promising option as it could be radiolabeled with 90 Y at room temperature with highest specific activity and demonstrated high in vitro stability in human serum and in presence of challenging metal ions commonly present in human plasma. The clearance pattern in Swiss mice revealed that 90 Y‐CHX‐ A″‐DTPA‐NCS cleared through the kidneys with minimum retention in any other major organ. Thus, the use of cyclohexyl‐DTPA based bifunctional chelators would increase the scope of making 90 Y‐labeled agents suitable for targeted therapy.