By the same token, significant challenges remain in renal vasculature mapping and hepatic imaging, where the majority of the blood supply is of venous origin.17 18 Delayed-phase imaging and perfusion kinetics have also been developed to characterize tumors using the well-known Patlak method.19 However, it has always been clear that better control over the pharmacokinetics, coupled with a longer circulation time for contrast agents,
would offer significant benefits. First, it would eliminate the need for high-speed scans because there would no longer be concerns about “missing” Inhibitors,research,lifescience,medical the bolus. Second, the delayed clearance would reduce acute renal load and probably reduce the incidence of CIN. Third, it would enable universal Inhibitors,research,lifescience,medical venography. One also imagines that with longer blood residence times, new delayed-phase imaging techniques would emerge. At short time scales, in just hours, one could enforce a constant input function and therefore increase the
precision of dynamic estimations. At long time scales, on the order of days, one envisions new dynamics hitherto unexplored because input functions have usually decayed to zero. All of these potential advantages have spurred significant interest in the development of long-circulating (“blood pool”) agents. Inhibitors,research,lifescience,medical The first foray into the development of nanoparticle blood pool agents happened in the 1980s.20 In a parallel development in the drug delivery field, the liposome, a bilayer bounded vesicle, was designed and built as a carrier for chemotherapeutic, antibiotic, and antifungal drugs.21–23 In the contrast agent arena, however, poor loading efficiency of the iodinated active molecule and rapid hepatic Inhibitors,research,lifescience,medical sequestration led to very limited success.24 25 A clinical trial of iodinated liposomes was terminated
due to adverse events.26 In the late 1990s, an iodinated triglyceride backbone was used to form triglyceride particles with long-circulating properties and enjoyed Inhibitors,research,lifescience,medical significant use in preclinical imaging.27 In the late 2000s, researchers developed an emulsion carrying iodinated molecules in its hydrophobic internal phase.28 While not strictly a long-circulating blood pool agent, this material does have a longer circulation time than conventional contrast agents. However, it is primarily intended to target macrophages and is being developed very for clinical use in tracking pathologies that accumulate macrophages,29 such as atherosclerotic plaques, certain tumors, and sites of inflammation and infection. A true blood pool agent (NCTX) has been designed and extensively tested by the authors of this paper. NCTX is a PEGylated liposomal particle containing clinically used, nonionic iodinated contrast agent (Figure 1). In 2002, the first in vivo AT13387 supplier experiments with this agent demonstrated cardiac imaging in a rabbit model using a 4-slice CT scanner.30 Since that landmark experiment, the agent has been successfully used to image the mouse vasculature in practically every anatomical region.