The finding of alternative imaging probes to Gadolinium (Gd) and other metal based contrast agents (CA) is crucial to overcome their established toxicity. Herein we describe the synthesis and characterization of an entirely organic metal-free magnetic resonance imaging (MRI) contrast agent based on polyphosphorhydrazone (PPH) dendrimers, fully functionalized with up to 48 organic nitroxide radical units. We propose an innovative synthetic procedure based on the use of an amino acid linker (Tyr) coupled to each dendrimer′s branch that permits the anchoring of the radicals and at the same time makes possible the control over their water solubility. We demonstrate that the negatively charged resulting PPH Gn-Tyr-PROXYL (n = 0–3) radical dendrimers are excellent candidates to be used as MRI contrast agents, suited for biomedical applications as they show high water solubility, no aggregation problems, and low cytotoxicity, as well as good stability in highly reducing environments. It is achieved a remarkable r 1 relaxivity, ca. four times higher (13 mM–1 s–1) than the gold-standard Gd-DTPA used in clinics. Furthermore, the r 1 and r 2 relaxivity per unit of radical showed an increase with the increase in generation of dendrimers.

Radiotherapy is one of the most commonly used cancer treatments, with an estimate of 40% success that could be improved further if more efficient targeting and retention of radiation at the tumor site were achieved. This review focuses on the use of dendrimers in radionanotherapy, an emerging technology aimed to improve the efficiency of radiotherapy by implementing nanovectorization, an already established praxis in drug delivery and diagnosis. The labeling of dendrimers with radionuclides also aims to reduce the dose of radiolabeled materials and, hence, their toxicity and tumor resistance. Examples of radiolabeled dendrimers with alpha, beta, and Auger electron emitters are commented, along with the use of dendrimers in boron neutron capture therapy (BNCT). The conjugation of radiolabeled dendrimers to monoclonal antibodies for a more efficient targeting and the application of dendrimers in gene delivery radiotherapy are also covered.