Engineering contrast agents for gastrointestinal magnetic particle imaging: The biological perspective

Abstract

Cancers of the gastrointestinal tract are one of the leading causes of death in affluent countries. Although they are usually curable if detected at an early enough stage, the compliance to undergo routine screenings for gastrointestinal cancers in a presymptomatic stage is low, mostly due to the discomfort which current diagnostic measures, such as gastroscopy, colonoscopy, digital rectal exams or feces examinations pose to the patient. Magnetic particle imaging (MPI) has the potential to overcome this hurdle as the procedure is noninvasive, radiation-free and assumed to be more sensitive than most other imaging modalities used today. Yet, MPI bears a catch as it requires special magnetizable contrast agents in the nanoscale range. These contrast agents have to meet a number of requirements. They must be detectable in the magnetic field, be manufacturable in a cost-effective manner, display a certain shelf life, be administrable in a compliant way, be stable in vivo, be specific and sensitive in labeling the neoplastic tissue and must not be harmful to the individual who incorporates them. Due to this complex requirement profile MPI contrast agent engineering lags behind imaging hardware development. In order to close in on this field it is important to identify, rate and define the relevant players which ingested MPI contrast agents have to deal with en route to their destination in the body. Potential players are the anatomy and microanatomy of the gastrointestinal tract, the chemical and biological composition of the luminal constituents as well as potential degradation and scavenger mechanisms. Once the possible impact of these factors has been established contrast agents can be designed to master these challenges. Yet, reaching the destination without causing harm is a necessary but not sufficient requirement. In order to fully exploit the potential of MPI and to qualify it for mass screening the method must be highly sensitive and specific. This may be achieved by targeting systems that direct the contrast agent exclusively and efficiently to the neoplastic tissue in question. In this paper we provide an overview on our current knowledge of the fate of magnetizable contrast agents in the gut, the players which determine this fate, measures to properly endow contrast agents for this task and means to equip them with the necessary specifity and sensitivity.