# Molecular Imaging with \({}^{68}\)Ga Radio-Nanomaterials: Shedding Light on Nanoparticles
## 1 Introduction  
Radiolabeled nanomaterials have emerged in the last years as a very promising tool for molecular imaging applications [1]. The combination of the size-dependent properties of nanomaterials with the sensitivity of radioisotopes in nuclear imaging techniques opens an attractive field in the development of new probes for the diagnosis and treatment of different pathologies. In terms of molecular imaging, the combined use of a radioisotope and a nanoparticle (NP) completely change the role of the latter. The possibility of using nanoparticles for in vivo \"hotspot\" imaging increases the usefulness of nanomaterials in biomedical imaging. For example, one of the reasons iron oxide nanoparticles have not replaced Gd-based agents in clinical practice is the typical dark contrast these nanoparticles provide. This can be a problem for many pathologies, where endogenous hypointense areas in magnetic resonance imaging (MRI) are common. The combination of this kind of nanomaterial with a radioisotope eliminates this limitation. This is the rationale behind the title we have chosen for our revision; the addition of a radioisotope to most nanomaterials sheds light on their utility as tracers in molecular imaging.  
Nanomaterials present an increased surface/volume ratio as one of their most exploited features. This particularity of materials at the nanometric scale, provides an enormous number of specific binding sites for multifunctionalization of nanomaterials with bioactive molecules for biomedical applications or other probes for multimodal imaging among multiple other possibilities. One of the reasons is the multiple combinations that emerge by just modifying three variables; type of nanomaterial, type of radioisotope and how the radioisotope is incorporated to the nanoparticle. Focusing on the last aspect, we can find surface radiolabeling, with or without a chelator, and core labeling. This last approach offers advantages concerning transmetallation and radioisotope detachment, at the cost of a more demanding synthesis, particularly time-wise when working with short half-life isotopes. In terms of type of nanomaterials and radioisotopes, almost all possible combinations have been achieved, although not all of them with the same practical usefulness from an imaging point of view. In the last years, it is easy to find examples with \({}^{18}\)F [2; 3; 4], \({}^{64}\)Cu [5; 6; 7], \({}^{69}\)Ge [8], \({}^{99m}\)Tc [9; 10], \({}^{123/124/125/131}\)I [11; 12; 13; 14; 15; 16], or even \({}^{11}\)C [17]. The new role of nanomaterials in imaging, by virtue of this combination, is probably the most important advantage; however, it is not limited to that. Other aspects benefiting from this \"marriage\" are related, for example, with a precise and quantitative study of nanoparticle biodistribution, a relatively easy tuning of tracer pharmacokinetics or the possibility of using radioisotopes for therapeutic purposes.  
The use of nanomaterials for nuclear imaging already has several important reviews summarizing the combination of different radioisotopes and nanoparticles [1; 18; 19; 20]. However, there are none focusing in what is becoming a well-liked sector of \({}^{68}\)Ga-labeled nanoparticles. In this review, we see what the main features of this radioisotope are, making it probably the most relevant one at present in the field.