Magnetic resonance
imaging (MRI) is one of the most sophisticated
diagnostic tools that is routinely used in clinical practice. Contrast
agents (CAs) are commonly exploited to afford much clearer images
of detectable organs and to reduce the risk of misdiagnosis caused
by limited MRI sensitivity. Currently, only a few gadolinium-based
CAs are approved for clinical use. Concerns about their toxicity remain,
and their administration is approved only under strict controls. Here,
we report the synthesis and validation of a manganese-based CA, namely,
Mn@HFn-RT. Manganese is an endogenous paramagnetic metal able to produce
a positive contrast like gadolinium, but it is thought to result in
less toxicity for the human body. Mn ions were efficiently loaded
inside the shell of a recombinant H-ferritin (HFn), which is selectively
recognized by the majority of human cancer cells through their transferrin
receptor 1. Mn@HFn-RT was characterized, showing excellent colloidal
stability, superior relaxivity, and a good safety profile. In vitro
experiments confirmed the ability of Mn@HFn-RT to efficiently and
selectively target breast cancer cells. In vivo, Mn@HFn-RT allowed
the direct detection of tumors by positive contrast enhancement in
a breast cancer murine model, using very low metal dosages and exhibiting
rapid clearance after diagnosis. Hence, Mn@HFn-RT is proposed as a
promising CA candidate to be developed for MRI.