Toward a Patient-Specific Traceable Quantification of SPECT/CT-Based Radiopharmaceutical Distributions

Quantitative SPECT/CT imaging is currently the state of the art for peritherapeutic monitoring of radiopharmaceutical distributions. Because of poor resolution, however, the verification of SPECT/CT-based activity distributions is of particular importance. Because of the lack of a ground truth in patient measurements, phantoms are commonly used as a substitute for clinical validation of quantitative SPECT/CT. Because of the time-consuming and erroneous preparation of multicompartment phantoms, such as for the kidney, the usually very complex internal activity distributions are typically replaced by 1- or 2-compartment models. To provide a simplified solution for generating inhomogeneous activity distributions, this work presents a methodology for designing single-compartment phantoms that mimic inhomogeneous spatial activity distributions by using internal filling structures of different volume fractions. Methods: A series of phantoms with different filling structures was designed, 3-dimensionally printed, and measured. After assessing the feasibility of the presented approach in a simple geometry, a set of three patient-specific kidney phantoms was designed on the basis of the contrast-enhanced CT scan of a patient with metastatic castration-resistant prostate cancer. Internal gyroid structures of different wall thicknesses were used in the renal medulla and cortex to reproduce the inhomogeneous activity distribution observed in a peritherapeutic SPECT/CT acquisition 24 h after injection of ¹⁷⁷Lu-labeled prostate-specific membrane antigen (apparent activity concentration ratios of 1:1, 1:3.5, and 1:7.5). After 3-dimensional printing, SPECT/CT experiments were performed and the results were compared with the patient data for different reconstruction settings (iterations, subsets, and postfiltering). Results: Good agreement was found between phantom designs and fabricated phantoms (based on high-resolution CT). No internal filling structures were visible in any of the SPECT images, indicating a sufficiently small feature size. Although good visual and quantitative agreement was achieved for certain combinations of filling structure and reconstruction, a histogram analysis indicated an even more complex activity distribution in the patient than represented by the two compartments assumed in our model. Conclusion: The proposed methodology provides patient-specific phantoms mimicking inhomogeneous activity distributions while using a single stock solution, thus simplifying the filling process and reducing uncertainties in the activity determination. This method enables an unprecedented possibility for patient-specific evaluation of radiopharmaceutical uptake, reducing uncertainties in internal dosimetry and individualized treatments.