Radiolabeling and PET–MRI microdosing of the experimental cancer therapeutic, MN-anti-miR10b, demonstrates delivery to metastatic lesions in a murine model of metastatic breast cancer

• Published in: Cancer nanotechnology Vol. 12; no. 1; pp. 1 - 15
• Main Authors: Le Fur, Mariane, Ross, Alana, Pantazopoulos, Pamela, Rotile, Nicholas, Zhou, Iris, Caravan, Peter, Medarova, Zdravka, Yoo, Byunghee
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 2021; Springer Nature B.V; BMC
• Subjects: Bioaccumulation; Biochemistry; Biocompatibility; Biodistribution; Biomedical Engineering and Bioengineering; Breast cancer; Cancer Research; Chemistry and Materials Science; Coinjection; In vivo methods and tests; Iron oxides; Lesions; Magnetic resonance imaging; Materials Science; Metastasis; MicroRNA; MR imaging; Nanoparticles; Nanotechnology; Organs; Positron emission; Positron emission tomography; Radiolabelling; Ribonucleic acid; RNA; RNA interference; Tomography; Toxicity; MicroRNA; RNA interference; MR imaging; Metastasis; Biodistribution; Positron emission tomography; microRNA; biodistribution; positron emission tomography; metastasis
• ISSN: 1868-6958; 1868-6966
• DOI: 10.1186/s12645-021-00089-5

Background In our earlier work, we identified microRNA-10b (miR10b) as a master regulator of the viability of metastatic tumor cells. This knowledge allowed us to design a miR10b-targeted therapeutic consisting of an anti-miR10b antagomir conjugated to ultrasmall iron oxide nanoparticles (MN), termed MN-anti-miR10b. In mouse models of breast cancer, we demonstrated that MN-anti-miR10b caused durable regressions of established metastases with no evidence of systemic toxicity. As a first step towards translating MN-anti-miR10b for the treatment of metastatic breast cancer, we needed to determine if MN-anti-miR10b, which is so effective in mice, will also accumulate in human metastases. Results In this study, we devised a method to efficiently radiolabel MN-anti-miR10b with Cu-64 ( 64 Cu) and evaluated the pharmacokinetics and biodistribution of the radiolabeled product at two different doses: a therapeutic dose, referred to as macrodose, corresponding to 64 Cu-MN-anti-miR10b co-injected with non-labeled MN-anti-miR10b, and a tracer-level dose of 64 Cu-MN-anti-miR10b, referred to as microdose. In addition, we evaluated the uptake of 64 Cu-MN-anti-miR10b by metastatic lesions using both in vivo and ex vivo positron emission tomography–magnetic resonance imaging (PET–MRI). A comparable distribution of the therapeutic was observed after administration of a microdose or macrodose. Uptake of the therapeutic by metastatic lymph nodes, lungs, and bone was also demonstrated by PET–MRI with a significantly higher PET signal than in the same organs devoid of metastatic lesions. Conclusion Our results demonstrate that PET–MRI following a microdose injection of the agent will accurately reflect the innate biodistribution of the therapeutic. The tools developed in the present study lay the groundwork for the clinical testing of MN-anti-miR10b and other similar therapeutics in patients with cancer.