Metal-free nitroxide-containing T1 magnetic resonance imaging contrast agent for invasive breast cancer diagnosis

Abstract

Magnetic resonance imaging (MRI) is one of the most useful methods for identifying tumours at an early stage, as well as monitoring tumours, owing to its noninvasive nature. Metal-based contrast agents (CA) are commonly practised for diagnostic purposes, but have confirmed toxicity profiles (e.g., non-curable nephrogenic systemic fibrosis, neurological abnormalities, etc.). Hence, it is necessary to develop non-toxic imaging probes. An efficient strategy for conjugating nitroxides onto the dendrimers’ surface using epoxides is suggested. In this research, we report a simpler conjugation pathway of nitroxides to a series of precise dendrimer scaffold poly(amidoamine) (PAMAM). Among the radical dendrimers, the third generation 3G-GT exhibits longitudinal relaxivity (r₁) of ca. 15.36 mM^-1s⁻¹ per molecule, which is exceptionally higher than metal-based CA Magnevist (3.2 mM^-1s⁻¹). 3G-GT has excellent features like superior reduction resistance and non-toxicity to living organisms. It shows attractive in vivo biodistribution as well as improved MRI contrast in breast cancer-bearing mice models, which supports the notion of the MRI CA application using the 3G-GT for early diagnosis of invasive breast cancer. Thus, the precise and stable radical dendrimers show good prospects as an alternative, metal-free MRI CA for tumour imaging.