Four novel chelators (L1–L4) and their 89zirconium complexes were prepared and compared with the 89zirconium desferrioxamine B (DFO) complex. The new chelates are based on 1,4,7,10-tetraazacyclododecane (cyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam) scaffolds and present either three or four hydroxamate arms for coordination with Zr4+ ions with coordination numbers between six and eight. The 89Zr–L4 complex showed similar stability to that of 89Zr–DFO when incubated in either rat blood plasma or ethylenediaminetetraacetic acid challenge experiments. Positron imaging and biodistribution studies in mice showed that 89Zr–L4 had similar pharmacokinetic behavior to that of 89Zr–DFO, with rapid renal elimination and low residual activity in background tissues. A bifunctional version of L4 (L5) was synthesized and conjugated to trastuzumab; an anti-HER2/neu antibody. Immunopositron emission tomography imaging and biodistribution with 89Zr–L5–trastuzumab revealed high tumor to background ratios (tumor/blood ratio: 14.2 ± 2.25) and a high tumor specificity that was comparable to the performance of 89Zr–DFO–trastuzumab.

We report the synthesis and MR relevant properties of CyPic3A, a heptadentate chelator that forms ternary Gd(III) complexes of hydration state q = 2. [Gd(CyPic3A)(H2O)2]− affords an r1 value of 5.70 mM−1s−1 at 1.41 T and 310 K and displays thermodynamic stability and kinetic inertness comparable to FDA approved MR imaging probes.