A systematic comparative evaluation of 90Y‐labeled bifunctional chelators for their use in targeted therapy

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 ⁹⁰Y 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 ⁹⁰Y 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 ⁹⁰Y‐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 ⁹⁰Y‐labeled agents suitable for targeted therapy.