###### Abstract
The biodistribution results indicated that even at the lowest concentration of P12, i.t. administrations resulted in higher accumulation in the lung and less in the liver. Intratumoral administration allowed P12 to target lung macrophages while i.v. and i.p. administrations did not. The other two routes of administration (i.v. and i.p.) presented higher accumulation of the injected substance in the liver and lymph nodes [12]. Therefore, it is crucial to select the appropriate administration route for nanostructures in order to achieve the optimum results. Another factor to consider when designing a nanoparticle is its shape. [PERSON] et al. investigated the in vivo behavior of nanostructures radiolabeled with \({}^{198}\)Au with different shapes, e.g., nanospheres, nanocages, nanodisks and nanorods. The radiolabeled nanospheres presented enhanced circulation in blood, the lowest clearance by the RES organs and the highest tumor uptake compared to the other three shapes. On the other hand, nanorods and nanocages could reach tumor cores, indicating a distinct advantage for the application of photothermal therapy. Nanostructures with different geometries (e.g., nanorods) can have different enhanced permeability and retention (EPR) effects due to changes in their in vivo properties such as blood circulation, the overcoming of various physiological barriers, and extravasation into the tumor [13]. Over the last decades, gold nanoparticles (AuNPs) have been extensively used for a wide range of applications, such as dual-modality imaging agents and theranostic agents, due to their unique properties, huge variety of sizes and shapes, ability to conjugate with various chemical groups, structural modification and low toxicity and biocompatibility not only in in vitro but also in vivo [14; 15; 16]. Furthermore, AuNPs can be used for photothermal therapy, a complementary approach for cancer treatment. This procedure is non-invasive, causing minimal functional disturbances [17]. Several studies have been conducted using AuNPs and radiolabeling with the gamma emitter \({}^{99\text{m}}\)Tc, which is the most commonly used radionuclide in diagnostic imaging. Inorder to achieve stable radiolabeling of AuNPs, sometimes it is necessary to first perform their functionalization with specific chemical groups (e.g., thiol groups) which will also allow conjugation with suitable radioisotopes. [PERSON] et al. investigated Au PENs (polyethylenimine-entrapped nanoparticles) radiolabeled with \({}^{99\text{m}}\)Tc after functionalization with APAS. The zeta potential of bare and APAS-modified Au PENs was measured under a range of different pH conditions in order to improve the cellular uptake. The results indicated that under slightly acidic environment, the tumor uptake was increased, leading to a promising contrast agent for dual SPECT/CT imaging [18]. [PERSON] et al. investigated the functionalization of AuNPs with HYNIC-GGC and c[RGDK-(C)] through interactions with the thiol groups of cysteine. After intravenous injection of the radiolabeled complex, the biodistribution results indicated high uptake in liver and spleen, which was significantly reduced after intraperitoneal administration. This is normal due to the fact that intravenously injected nanoparticles lead to a substantial uptake by the macrophages present in liver and spleen [19]. On the other hand, it was demonstrated by several studies that intraperitoneal injection results in a minimal uptake of AuNPs by Kupffer cells in liver [20]. [PERSON] et al. evaluated AuNPs functionalized with polyamidoamine dendrimers (PAMAM) in a murine HeLa xenograft tumor model which presented high uptake in spleen, lung, liver and kidney compared to tumor [21]. [PERSON] et al. studied AuNPs functionalized with dithiolated DTPA (DTDTPA) and radiolabeled with \({}^{99\text{m}}\)Tc and they investigated their in vivo behavior in healthy rats.