Preclinical Imaging Evaluation of miRNAs’ Delivery and Effects in Breast Cancer Mouse Models: A Systematic Review

Background: We have conducted a systematic review focusing on the advancements in preclinical molecular imaging to study the delivery and therapeutic efficacy of miRNAs in mouse models of breast cancer. Methods: A systematic review of English articles published in peer-reviewed journals using PubMed, EMBASE, BIOSIS™ and Scopus was performed. Search terms included breast cancer, mouse, mice, microRNA(s) and miRNA(s). Results: From a total of 2073 records, our final data extraction was from 114 manuscripts. The most frequently used murine genetic background was Balb/C (46.7%). The most frequently used model was the IV metastatic model (46.8%), which was obtained via intravenous injection (68.9%) in the tail vein. Bioluminescence was the most used frequently used tool (64%), and was used as a surrogate for tumor growth for efficacy treatment or for the evaluation of tumorigenicity in miRNA-transfected cells (29.9%); for tracking, evaluation of engraftment and for response to therapy in metastatic models (50.6%). Conclusions: This review provides a systematic and focused analysis of all the information available and related to the imaging protocols with which to test miRNA therapy in an in vivo mice model of breast cancer, and has the purpose of providing an important tool to suggest the best preclinical imaging protocol based on available evidence.

Preclinical Imaging Evaluation of MiRNAs Delivery and Effects in Breast Cancer Mouse Models: A Systematic Review

Background: miRNAs have been defined as a tumor suppressor or oncogene (oncomiR) in several human cancers. We have conducted a systematic review highlighting and specifically focusing in the advancements in preclinical molecular imaging to study in vivo the delivery and the therapeutic efficacy of miRNAs in mouse models of breast cancer.Methods: A systematic review of English articles published in peer-reviewed journals using PubMed® (including MEDLINE®), EMBASE, BIOSIS™, Scopus was performed. Search terms included breast cancer, mouse, mice, microRNA(s) and miRNA(s). The search was focused on the last five years (2015-2021). All studies using miRNA in breast cancer models which included a preclinical imaging evaluation, both in vivo or ex vivo were analyzed. Result: From a total of 2,073 records, 1,221 papers were assessed for full text eligibility, but excluding all those in which there was no use of mouse models of breast cancer, there was not in vivo imaging or ex vivo on whole organs, and without a clear link to a miRNA, our final data extraction was made on a total of 114 manuscripts. The murine genetic background most used in miRNA studies have been resulted to be the Balb/C (46,7%). Regarding cell lines, MDA-MB-231 parental and derived cells were used in most experiments (62,5%). The most used model was the i.v. metastatic model (46,8%), which was obtained via intravenous injection (68,9%) in the tail vein. The modulation of miRNA was obtained mainly by stable transfection with specific lentiviral plasmid or DNA constructs in luciferase- labelled BC cells (54,4%). Bioluminescence resulted the most used tool (64%) and was used as a surrogate of tumor growth for efficacy treatment or for the evaluation of tumorigenicity in miRNA transfected cells (29,9%); for tracking, evaluation of engraftment and for response to therapy in metastatic models (50,6%).Conclusion: this review provides a systematic and focused analysis of all the information currently available and related to the imaging protocols to test miRNA therapy in in vivo mice model of BC and has the purpose to provide an important tool to suggest the best pre-clinical imaging protocol on currently available evidences.

Development of a High-resolution SSR-SPECT System for Preclinical Imaging and Neuroimaging

The utility of animal models in preclinical research has been increasing by the availability of methods for in vivo imaging. In particular, techniques like single photon emission computed tomography (SPECT) show high potential, which is usually limited by spatial resolution. This represents an important parameter influencing scanner design, given the small size of the anatomical structures to be investigated. The purpose of the present work was to assess the performance of a scintigraphic system with improved spatial resolution based on our previous detector by applying the Super Spatial Resolution (SSR). Our dual-head SPECT system is composed of gamma cameras based on the Hamamatsu H13700 position-sensitive photomultiplier tube (PSPMT). In each detector head, the PSPMT is coupled to a 28×28 array of CRY018 scintillation crystals. The pure Tungsten parallel square hole collimator ensures the position sensitivity, and a dedicated resistive chain readout so as an ADC board have been proprietary designed. To finalize the mechanical development of the SSR-SPECT system several tests were carried out. Based on the results obtained in the test phase, a partial review of the mechanical design was performed. Then a dedicated machine handling software was developed, and in particular, a kinematic software debugging and testing was assessed. Finally, several experiments were carried out by using Derenzo phantoms and capillaries filled with radioactive sources. Finally, the performance of our system was evaluated performing small animal imaging studies. The SPECT spatial resolution was experimentally determined to be about 1.6 mm. We reach a resolution of 1.18 mm by applying the SSR based on two images. The results of this study demonstrated the good capability of the system as a suitable tool for preclinical imaging especially in fields like neuroscience for the study of small brain structures.