Author: Adedamola Adeniyi, Bryan Bednarz, Malick Bio Idrissou, Reinier Hernandez, Ohyun Kwon, Brian W. Miller, Zachary S Morris, Maya Takashima, Jamey Weichert 👨🔬
Affiliation: Departments of Radiation Oncology and Medical Imaging, University of Arizona, Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin - Madison, Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin–Madison, Department of Radiology, School of Medicine and Public Health, University of Wisconsin–Madison, Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin–Madison 🌍
Purpose: As radiopharmaceutical therapy (RPT) becomes more prevalent in clinical applications, understanding dose-response relationships in the tumor microenvironment (TME) and normal tissues is essential for improving therapeutic outcomes. While image-based RPT dosimetry with modalities like µSPECT/CT is common, their voxel-level spatial resolution limits sub-organ analysis. However, digital autoradiography with multiple slices can provide high-resolution 3D activity distributions within TME and tissue samples. This study developed a preclinical multiscale dosimetry approach for RPT using 177Lu by integrating µSPECT/CT (U-SPECT MiLabs) with an ionizing-radiation quantum imaging detector (iQID).
Methods: Calibration of 177Lu for iQID was performed using a Gadox-based scintillating phosphor screen (BioMax TranScreen). A mouse bearing B16-mixed (poor immunogenic melanoma) flank tumor xenografts was injected with 519.9 µCi of 177Lu-PNT6555, delivering low, heterogeneous doses. In vivo µSPECT/CT imaging was conducted at 3, 24, and 95 hours post-injection, followed by ex vivo imaging at 110 hours. Subsequently, iQID imaging of 38 tumor slices (20 µm thickness) was performed and registered to corresponding microscopic images. The Monte Carlo dosimetry platform RAPID quantified absorbed dose rates from the imaging data. Pharmacokinetic parameters from µSPECT/CT enabled estimation of total integrated absorbed doses for iQID data.
Results: A linear calibration curve (y = 1.7075x–20.608, R2 = 0.9985) converted counts-per-second to activity (Bq). The pharmacokinetic curve fitted an exponential uptake (y = 8.11×10-4×[e^(-3.38×10-2t)–e^(-1.63t)], R2 = 0.954). The mean absorbed dose (Gy/MBq) of in vivo µSPECT/CT was 0.0235, whereas ex vivo µSPECT/CT and iQID were 0.0224 and 0.0241, respectively. Dose-volume histograms were generated to evaluate the dose heterogeneity in tumor samples.
Conclusion: This study demonstrates a practical multiscale RPT dosimetry framework using 177Lu and calibrated iQID imaging. Future research will leverage this high-resolution approach to correlate dose distributions with diverse biological responses in both preclinical models and early-phase clinical trials, facilitating improved image-based dosimetry modeling for later-phase studies.