MUC1, the transmembrane glycoprotein Mucin 1, is usually found to be overexpressed in a variety of epithelial cancers playing an important role in disease progression. MUC1 isoforms such as MUC1/Y, which lacks the entire variable number of tandem repeat region, are involved in oncogenic processes by enhancing tumour initiation. MUC1/Y is therefore considered a promising target for the identification and treatment of epithelial cancers; but so far, the precise role of MUC1/Y remains to be elucidated. In this work, we developed and identified a DNA aptamer that specifically recognizes the splice variant MUC1/Y for the first time. The DNA aptamer could bind to a wide variety of human cancer cells, and treatment of MUC1/Y positive cells resulted in reduced growth in vitro. Moreover, MUC1/Y aptamer inhibited the tumour growth of breast cancer cells in vivo. The present study highlights the importance of targeting MUC1/Y for cancer treatment and unravels the suitability of a DNA aptamer to act as a new therapeutic tool.

New forms of cancer treatment, which are effective, have simple manufacturing processes, and easily transportable, are of the utmost necessity. In this work, a methodology for the synthesis of radioactive Gold-198 nanoparticles without the use of surfactants was described. The nuclear activated Gold-198 foils were transformed into H¹⁹⁸AuCl₄ by dissolution using aqua regia, following a set of steps in a specially designed leak-tight setup. Gold-198 nanoparticles were synthesized using a citrate reduction stabilized with PEG. In addition, TEM results for the non-radioactive product presented an average size of 11.0 nm. The DLS and results for the radioactive ¹⁹⁸AuNPs presented an average size of 8.7 nm. Moreover, the DLS results for the PEG-¹⁹⁸AuNPs presented a 32.6 nm average size. Cell line tests showed no cytotoxic effect in any period and the concentrations were evaluated. Furthermore, in vivo testing showed a high biological uptake in the tumor and a cancer growth arrest.

The oncogene HER2 is an important molecular target in oncology because it is associated with aggressive disease and the worst prognosis. The development of non-invasive imaging techniques and target therapies using monoclonal antibodies is a rapidly developing field. Thus, this work proposes the study of the radioimmunotheranostic pair, [¹¹¹In]In-DTPA-trastuzumab and [¹⁷⁷Lu]Lu-DOTA-trastuzumab, evaluating the influence of the chelating agents and radionuclides on the biological properties of the radioimmunoconjugates (RICs). The trastuzumab was immunoconjugated with the chelators DTPA and DOTA and radiolabeled with [¹¹¹In]InCl₃ and [¹⁷⁷Lu]LuCl₃, respectively. The stability of the RICs was evaluated in serum, and the immunoreactive and internalization fractions were determined in SK-BR-3 breast cancer cells. The in vivo pharmacokinetics and dosimetry quantification and the ex vivo biodistribution were performed in normal and SK-BR-3 tumor-bearing mice. The data showed that there was no influence of the chelating agents and radionuclides on the immunoreactive and internalization fractions of RICs. In contrast, they influenced the stability of RICs in serum, as well as the pharmacokinetics, dosimetry and biodistribution profiles. Therefore, the results showed that the nature of the chelating agent and radionuclide could influence the biological properties of the radioimmunotheranostic pair.

Losartan is widely used in clinics to treat cardiovascular related diseases by selectively blocking the angiotensin II type 1 receptors (AT₁Rs), which regulate the renin-angiotensin system (RAS). Therefore, monitoring the physiological and pathological biodistribution of AT₁R using positron emission tomography (PET) might be a valuable tool to assess the functionality of RAS. Herein, we describe the synthesis and characterization of two novel losartan derivatives PET tracers, [¹⁸F]fluoroethyl-losartan ([¹⁸F]FEtLos) and [¹⁸F]ammoniomethyltrifluoroborate-losartan ([¹⁸F]AMBF₃Los). [¹⁸F]FEtLos was radiolabeled by ¹⁸F-fluoroalkylation of losartan potassium using the prosthetic group 2-[¹⁸F]fluoroethyl tosylate; whereas [¹⁸F]AMBF₃Los was prepared following an one-step ¹⁸F-¹⁹F isotopic exchange reaction, in an overall yield of 2.7 ± 0.9% and 11 ± 4%, respectively, with high radiochemical purity (>95%). Binding competition assays in AT₁R-expressing membranes showed that AMBF₃Los presented an almost equivalent binding affinity (K_i 7.9 nM) as the cold reference Losartan (K_i 1.5 nM), unlike FEtLos (K_i 2000 nM). In vitro and in vivo assays showed that [¹⁸F]AMBF₃Los displayed a good binding affinity for AT₁R-overexpressing CHO cells and was able to specifically bind to renal AT₁R. Hence, our data demonstrate [¹⁸F]AMBF₃Los as a new tool for PET imaging of AT₁R with possible applications for the diagnosis of cardiovascular, inflammatory and cancer diseases.