Speaker
Description
Background. Spatial heterogeneity of radiotracer distribution within the tumour microenvironment is a primary determinant of radiopharmaceutical therapy (RPT) efficacy and normal-tissue toxicity. Quantifying this heterogeneity in living tissue at the mesoscale the biologically relevant length scale of 50–500 μm that encompasses individual micro-vessels, hypoxic gradients, and receptor-expression boundaries remains inaccessible to current measurement methods. Clinical PET and SPECT provide in vivo compatibility but are limited to millimetre-scale spatial resolution; digital autoradiography offers sub-100 μm resolution in fixed thin sections but requires tissue sacrifice, hours-long exposures incompatible with kinetic measurement, and suffers substantial resolution degradation at physiologically relevant specimen thicknesses. The Intravital Theranostic Imaging Camera (ITIC) is a single-particle ionizing-radiation quantum imaging system developed to address this methodological gap.
Methods. ITIC detects individual beta particles through event-by-event quantum acquisition: each particle interaction in a thin scintillation screen generates a spatially localised flash of light that is amplified by a dual-stage microchannel plate (MCP) image intensifier and recorded by a scientific CMOS sensor as a list-mode entry encoding position, timestamp, and energy. System performance was comprehensively characterised by multi-modal comparison against gamma counting and phosphor-plate autoradiography using ¹⁸F calibration standards and heterogeneous biological leaf phantoms with activity contrasts mimicking the tumour and its microenvironment. Spatial resolution was independently validated against optical microscopy ground truth by two complementary analysis frameworks. A GEANT4 Monte Carlo simulation established the empirical FWHM-versus-tissue-thickness transfer function across the full intravital window chamber thickness range. Temporal and dosimetric performance was assessed through longitudinal ¹⁷⁷Lu-PSMA imaging of ex vivo human prostate cancer xenograft tissue over six days.
Results. ITIC achieved quantitative accuracy comparable to gamma counting, with systematic errors under 5% in the entire activity range. In addition, spatial resolution of 115 ± 31 μm FWHM was achieved in biological phantoms mimicking tissue thicknesses relevant to intravital imaging, with the whole image acquisition taking 15-30 minutes, as opposed to 4-12 hours required for autoradiography. More importantly, while the resolution of autoradiography falls off to 150-250 μm in specimens thicker than 100 μm, the resolution of ITIC remains the same even in tissue phantoms of 200-400 μm, which are directly compatible with the dorsal window chamber geometries that are used for intravital imaging. The Monte Carlo-derived FWHM-versus-tissue-thickness transfer function, the first empirical model of its kind for beta-particle imaging through soft tissue, quantified resolution across three physically distinct regimes and provides a principled basis for intravital experimental design at any window chamber thickness. Longitudinal 177Lu imaging showed spatial heterogeneity patterns that were stable (tissue contour plot) while the decay kinetics were in line with the physical half-life, thereby confirming the count-rate measurement pipeline as the quantitative baseline for future dose-point-kernel convolution to absorbed dose maps. As an initial sign of more dosimetric capabilities, time-resolved count-rate curves retrieved from spatially different tissue compartments, high-uptake tumour and low-uptake parenchyma, displayed physically consistent independent decay behaviour, implying that ITIC has the spatial specificity and temporal resolution to enable spatially resolved microdosimetry in future dedicated studies.
Conclusion. ITIC is an imaging system that can perform quantitative, real-time radiopharmaceutical imaging of living tissue at the mesoscale, the spatial scale at which the therapeutic outcome is determined. This characterization is the quantitative basis for window chamber studies, which allow direct, longitudinal observation of radiotracer distribution, uptake kinetics, and dose heterogeneity within tumour and its microenvironment in a living organism. These are measurements that require the simultaneous combination of spatial resolution, temporal continuity, and biological compatibility that ITIC uniquely brings together as an integrated intravital platform.
| Track | PSMR |
|---|---|
| Presentation type | Oral |