In vivo Imaging Biodistribution Profile of a New Macrocyclic Gadolinium Chelate as a Highly Stable Multifunctional MRI Contrast Agent

ABSTRACT

Gadolinium contrast agents (CAs) are integral components of clinical magnetic resonance imaging (MRI). However, safety concerns have arisen regarding the use of gadolinium CAs, due to their association with nephrogenic systemic fibrosis (NSF). Furthermore, recently the long-term retention of Gd²⁺-based CAs in brains patients with normal renal function raised another possible safety issue. The safety concerns of Gd²⁺-based CAs have been based on the ligand structure of Gd²⁺-based CAs, and findings that Gd²⁺-based CAs with linear ligand structures showed much higher incidences of NSF and brain retention of CAs than Gd²⁺-based CAs with macrocyclic ligand structure. In the current study, we report the in vivo biodistribution profile of a new highly stable multifunctional Gd²⁺-based CA, with macrocyclic ligand structure (HNP-2006). MR imaging using HNP-2006 demonstrated a significant contrast enhancement in many different organs. Furthermore, the contrast enhanced tumor imaging using HNP-2006 confirmed that this new macrocyclic CA can be used for detecting tumor in the central nervous system. Therefore, this new multifunctional HNP-2006 with macrocyclic ligand structure shows great promise for whole-body clinical application.