In vivo imaging of blood flow dynamics and cell migration in tumour microvasculature via real-time single nanoparticle tracking with positrons

forthcoming

The tumour microvasculature consists of a disorganised network of immature blood vessels with aberrant dynamics and high permeability, which play a critical role in tumour growth, metastasis, and resistance to therapy. Despite its importance, studying blood flow dynamics and cell migration within this environment remains challenging due to the microvasculature's complexity, minute size, and structural irregularities. Positron emission particle tracking (PEPT), a technique that tracks a single particle radiolabelled with a positron emitter in real-time and 3D, offers a transformative solution to investigate such intricate systems. Widely used in industry to study complex flow dynamics, PEPT´s potential for biomedical applications remains untapped due to the lack of compatible single-particle tracers with sufficient radioactivity, nanoscale dimensions, and the ability to evade rapid sequestration. I hypothesise that by overcoming these barriers, PEPT will provide unprecedented insights into blood flow dynamics and cell migration in tumour microenvironments. NanoFLOW aims to bridge this gap by integrating finely tuned single nanoparticle-based nanomedicines with advanced imaging technology. This project has four main objectives: i) To engineer nanoparticles with extended circulation times and tumour cell-targeting capabilities; ii) To achieve exceedingly high specific activity radiolabelled nanoparticles; iii) To develop microfluidic-based methods for accurate quantification and isolation of single nanoparticles; and iv) To validate PEPT in a fibrosarcoma mouse model. By addressing critical challenges in the application of nanomedicines, NanoFLOW will provide ground-breaking insights into tumour progression and metastasis, redefining the boundaries of nanomedicine and setting a new benchmark in cancer imaging and diagnostic precision with far-reaching implications for related fields including drug delivery, molecular imaging and image-guided therapy.