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Abstract Background Previous studies with polymeric micelles using molecular imaging for the in vivo study and nanosystem characterization leads us to develop radionanoprobes for the diagnosis and monitoring of interventions in preclinical research with animal models of breast and colon cancer. Considering the possibility of translation to the clinic, the choice of 99mTc to label the nanoprobes is its availability and the widespread SPECT distribution in the region. From the radiochemical point of view, using a direct labeling technique analogous to the cold reagent sets widely used in the clinic would help its translation. Soluplus® is an attractive polymer for synthesizing micelles that also allows their functionalization. With all the above, the objective of this work was to design, develop and characterize nanoprobes based on polymeric micelles and radiolabeled with 99mTc for the characterization of biological processes linked to the diagnosis, prognosis and monitoring of oncological pathologies in preclinical research using molecular images. Results 4 radionanoprobes (99mTcTc-Soluplus®, 99mTcTc-Soluplus®+TPGS, 99mTcTc-Soluplus®+glucose and 99mTcTc-Soluplus®+bevacizumab) were obtained with high radiochemical purity (> 95% in all cases) and with stability in murine serum up to 3 hours of incubation. The systems maintained the 100 nm size of the Soluplus® polymeric micelles even when they were functionalized and labeled with 99mTc. The image acquisition protocol allowed the visualization of tumor uptake in two cancer experimental models with the radionanoprobes assigned by group where the signal/background ratio found in the in vivo biological characterization showed values of 1.7 for 99mTcTc-Soluplus®+TPGS; 1.8 for 99mTcTc-Soluplus®; 2.3 for 99mTcTc-Soluplus®+glucose in the breast cancer model and 1.8 for 99mTcTc-Soluplus® and 3.3 for 99mTcTc-Soluplus®+bevacizumab in the colon cancer model. The results were validated through ex vivo biodistribution, observing that the uptake of the tumors, regardless of the model, is moderate while the concentration of activity in the blood is higher, suggesting that the enhanced permeability and retention effect (EPR) would be one of the mechanisms involved in imaging tumors in addition to the active targeting of radionanoprobes. Conclusions the polymeric micelles synthesized with Soluplus® constitute an attractive nanotechnological platform for the development of radionanoprobes that allow the monitoring of experimentation in animal models in oncology.
Salgueiro et al. (Tue,) studied this question.